© 1998 American Heart Association, Inc.
Original Contributions |
Age-Related Deterioration in Arterial Structure and Function in Postmenopausal Women
Impact of Hormone Replacement Therapy
From the Department of Medicine, Monash University, Monash Medical Centre, Clayton (B.P.M., Y.-L.L., H.T., L.M.S.); the Department of Biomedical Engineering, La Trobe University, Bundoora (J.D.C.); and Baker Medical Research Institute, Prahran, Melbourne (A.D.), Australia.
Correspondence to Associate Professor Barry McGrath, Cardiovascular Research Unit, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, 3168 Australia. E-mail barry.mcgrath{at}med.monash.edu.au
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Abstract |
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Abstract—Epidemiological evidence suggests that hormone replacement therapy (HRT) reduces morbidity and mortality from cardiovascular diseases in postmenopausal women. In this study, indices of arterial function [total systemic arterial compliance (SAC) and carotid arterial distensibility coefficient (DC)], structure [carotid intima-media thickness (IMT)], and lipid profiles were compared in postmenopausal women on long-term HRT and aged-matched controls. One hundred nine women aged 44 to 77 years taking HRT and an age-matched group of 108 female controls were entered into the study. The two groups were similar for body mass index, smoking status, exercise level, alcohol intake, and blood pressure. Fasting cholesterol, low density lipoprotein, and lipoprotein(a) were reduced and high density lipoprotein increased in the HRT group. IMT increased with age; SAC and DC were reduced with age in both groups. The HRT group had a higher mean SAC (0.42±0.02 versus 0.34±0.02 U/mm Hg, P=0.0001) and a lower mean IMT (0.67±0.01 versus 0.74±0.02 mm, P=0.006) than did controls. Subgroup analysis for estrogen versus estrogen plus progestin revealed no differences for SAC and IMT; DC, however, was greater in estrogen-only users. Smokers on HRT had a higher mean SAC (0.41±0.02 versus 0.31±0.01 U/mm Hg, P=0.008) and a lower IMT (0.65±0.02 versus 0.75±0.03 mm, P=0.002) than did smokers not taking such therapy. A protective effect of long-term estrogen therapy on age-related changes in arterial structure and function in postmenopausal women was evident in smokers and nonsmokers alike. Progestin appeared to counteract the effects of estrogen on carotid compliance only. Long-term controlled trials are needed to determine the significance of these findings.
Key Words: arterial compliance • carotid intima-media thickness • estrogen • progestins • postmenopausal
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Introduction |
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A number of case-control, cohort, and cross-sectional studies have suggested that the potential beneficial effects of HRT in postmenopausal women for reducing the relative risk of cardiovascular disease are in the range of 40% to 50%.1 2 3 4 5 Results are still pending from long-term, prospective, controlled trials to substantiate a role for HRT in reducing cardiovascular morbidity and mortality in postmenopausal women. Many mechanisms have been proposed for estrogen's effects on the rate of progression of atherosclerotic vascular disease.5 6 7 8 9 10 11 12 13 Estrogen therapy reduces LDL cholesterol and increases HDL cholesterol.5 7 It may also inhibit lipoprotein oxidation8 and inhibit proliferation of smooth muscle cells in arterial walls.9 10 Atherosclerotic plaque formation in arteries was reduced by estrogen therapy compared with placebo in cholesterol-fed rabbits11 and monkeys on a high-fat diet.12 Estrogen therapy alone or in combination with a progestin similarly limited atherosclerotic plaque development in experimental animals.13
Indices of arterial wall structure and function that can be measured by noninvasive techniques in humans include carotid wall IMT and arterial compliance. Arterial wall IMT is influenced by known cardiovascular risk factors14 and is a useful surrogate marker of coronary arterial disease.15 Arterial compliance is significantly correlated with factors known to affect the stiffness of arteries, such as age, hypertension, diabetes, and atherosclerotic vascular disease.16 17 18 19 20 21 22
In this study, we determined the indices of vascular function (systemic and carotid arterial compliance) and of vascular structure (carotid arterial IMT) in a large group of postmenopausal women receiving HRT for at least 1 year and in an aged-matched control group not on HRT. The impact of age on these vascular parameters and the effects of estrogen or estrogen plus progestin intervention on age-related changes in vascular health were studied.
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Methods |
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Two hundred seventeen postmenopausal women were recruited for the study from an urban population in Melbourne, Australia. All subjects had been postmenopausal for at least 2 years. One hundred nine subjects were taking HRT, 57 on estrogen alone (primarily Premarin) and 52 on estrogen plus progestin therapy (primarily Provera). An age-matched group of 108 women not on HRT was also studied. Each subject completed a questionnaire to assess cardiovascular risk factors based on the National Heart Foundation of Australia Risk Factor Prevalence study.23 The prevalence of smokers in the study (41%) was greater than that for women of equivalent age in the Australian community (22%), as a number of subjects who volunteered were participants in a separate study of male and female smokers at the study center.
The study protocol was approved by the Human Research and Ethics Committee, Monash Medical Center, Melbourne. Informed consent was obtained from all subjects. They were also advised not to take caffeine-containing drinks for at least 8 hours before vascular ultrasound measurements, which were performed in a quiet, air-conditioned clinical laboratory after the subjects had been resting in the supine position for at least 10 minutes. Serum samples for lipid profile analysis were collected after an 8-hour fast.
Total SAC
In all 217 subjects, as depicted in Figure 1
, SAC was estimated by the "area
method," which requires measurement of volumetric blood flow and
associated driving pressure to derive an estimated compliance over the
total systemic arterial tree.17 24 A
3.5-MHz continuous-wave Doppler flow velocimeter
(Multidoplex MD1, Huntleigh Technology) was placed on the suprasternal
notch to estimate ascending aortic blood flow. Aortic driving pressure
was estimated by applanation tonometry of the carotid artery by using a
noninvasive pressure transducer (Millar Mikro-tip, Millar Instruments).
The pressures obtained by this method were calibrated against brachial
artery pressure measurements by using a Dinamap device (CRITIKON 1846
SX).
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The formulas used for calculation of SAC were as follows:
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The formula for estimation of r from BSA was based on the work of Roman et al25 and data from our own laboratory. In all subjects enrolled in this study, calculated SAC values were derived from estimated aortic root diameter (SACBSA). These were compared with SACecho, an alternative methodology based on echocardiographic assessment of the aortic root diameter. There was very close agreement between SACBSA and SACecho (r=0.91, n=56, P<0.001). A Bland-Altman plot26 showed no significant trend with increasing SAC.
Repeatability of the SAC measurements was assessed in a subgroup of the
study population. Twenty-eight subjects attended the study center on 2
separate occasions 2 to 4 weeks apart without changing any therapy or
lifestyle features over the interval. The correlation coefficient for
SAC between the 2 visits was 0.74; the coefficient of variation was
11.2%; the mean difference±SD was 0.05±0.14 U/mm Hg; and the
coefficient of repeatability was 0.28. These results are similar to
those previously reported using the same
technique.27 Kupari and
colleagues18 used magnetic resonance techniques
to assess the elastic modulus of the ascending aorta, with a
repeatability of 
20%.
Ultrasound Imaging
One hundred fifty-five subjects, 78 on HRT and 77 not on HRT,
were further investigated with lipid profiles and an imaging study of
the common carotid arteries. This was performed by using a
high-resolution ultrasound machine (Diasonics DRF-400) with a 7.5-MHz
mechanical sector transducer (7.5-SPC). A region 1 cm proximal to the
origin of the bulb of the right common carotid artery was identified by
B-mode ultrasonography. Of all sites that have been used in ultrasound
studies for the assessment of IMT, this region has been demonstrated to
provide the most reproducible results when measurements are performed
in more than 1 direction.28 The transducer was
manipulated so that the near wall of the carotid artery was parallel to
the transducer footprint and the lumen was maximized in the
longitudinal plane for both B-mode imaging and M-mode
recording. Three images of each B-mode, taken from different
angles (anterior, anterolateral, and lateral), and 5 images of each
M-mode were recorded. The images were digitized and
saved on computer via a customized computer program using A House of
Windows software (C. Smith, Auckland, New Zealand) as previously
described.29 Brachial BP recordings were
taken at 5-minute intervals throughout the period of ultrasound imaging
by using a Dinamap device (CRITIKON 1846 SX).
Image Analysis
A B-mode scan of an artery is characterized by two echogenic
lines (known as leading edges) separated by a hypoechogenic space.
Based on the work of Pignoli and colleagues,30 it
has become accepted, though not without
challenge,31 that the outer line corresponds
anatomically to the media-adventitia interface. It is generally agreed
that the inner line corresponds to the lumen-intima interface. The
distance between the two lines thus represents the IMT. The
results for IMT and carotid diameter changes for assessing carotid
compliance were analyzed by using the customized A House of
Windows software program as previously
reported.29 Each image was recalled
(magnification x5), and the distance between two successive R waves
was determined from the ECG tracing. A 1-cm longitudinal section of the
image of the common carotid artery was divided into 10 equal segments
by using a computer-generated grid, and the investigator was able to
select media-adventitia and lumen-intima interfaces for the near and
far walls of the carotid artery by positioning a cursor at each
intersection where a grid line crossed the vessel wall. The cursor
could move freely in the vertical but not in any other direction.
Measurements were automatically transferred and saved in a database
(Quest for Windows, version 2.1). Only the IMT measurements for the far
wall of the right common carotid artery were used for the data
analysis in this study.
Two parameters were estimated: (1) right common carotid arterial far-wall IMT and (2) the DC, a measure of the change in carotid artery cross-sectional area for a change in BP relative to its initial cross-sectional area.
The formula for calculation of carotid compliance was as follows:
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D is
change in diameter of the distal common carotid artery; D is
diastolic diameter; and P is the difference
between average systolic and average diastolic
carotid BPs. Carotid BP was the carotid pressure waveform obtained by
applanation tonometry and scaled by linear interpolation from measured
mean end-diastolic BPs.22 The repeatability of these measurements was assessed in a subgroup of the study population. A single investigator (L.M.S.) performed all IMT and carotid wall compliance measurements. Twenty-nine subjects attended the study center on 2 separate occasions 2 to 4 weeks apart, without having changed any therapy or lifestyle features over the interval. The correlation coefficient for IMT between the 2 visits was 0.92; the coefficient of variation was 5.6%; the mean difference±SD was 0.03±0.01 mm; and the coefficient of repeatability was 0.02. A Bland-Altman plot26 showed no significant trend with increasing IMT.
Lipid Measurements
Fasting venous blood samples for total cholesterol
and triglyceride measurements were collected from all 155
subjects who underwent both SAC and carotid imaging studies. Fifty
percent of these subjects were randomly selected for additional fasting
HDL cholesterol, LDL cholesterol, and Lp(a)
measurements.
Statistical Analysis
Student's unpaired t test was used to compare
differences in mean values for group characteristics, lipids,
arterial compliance, and carotid IMT measurements for HRT
and non-HRT groups. All measurements except those for Lp(a) were
normally distributed. Differences between groups for Lp(a) were
assessed by nonparametric statistical methods. Two subgroup
analyses were performed: (1) subjects who were being treated
with estrogen alone versus those who were being treated with estrogen
plus progestin and (2) smokers versus nonsmokers. Linear regression
analysis was used to examine the relationships between indices
of arterial compliance, IMT, and age. A multiple linear
regression model was developed to analyze relationships between
HRT, cardiovascular risk factors, and vascular
parameters. ANOVA and ANCOVA were used to adjust for
interactions between variables. Data are given as mean±SEM.
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Results |
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The HRT and non-HRT groups were not significantly different for weight, height, BMI, smoking status, BP, alcohol intake, and exercise (Table 1
). Ten subjects in each group
were on antihypertensive medications. Four subjects in the non-HRT
group had mean BP readings >160 mm Hg systolic or
90 mm Hg diastolic after 3 readings at rest. In the
subgroup analysis smokers were slightly but significantly older
than nonsmokers, with the groups otherwise well matched (Table 2). Duration of therapy was similar in
the estrogen and combined-therapy groups (88±10 versus 70±7 months,
P=NS), as it was in the smokers compared with nonsmokers
(79±11 versus 80±2 months, P=NS).
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The results for the plasma lipids in the HRT and control groups are
shown in Figure 2. Mean plasma total and
LDL cholesterol were significantly lower and mean HDL
cholesterol significantly increased in the HRT group
compared with controls. Mean values for triglyceride were
not significantly different in the two groups. Lp(a) analyzed
by nonparametric measures was lower in the HRT group
(202±39 versus 357±58 mg/L, P=0.04). Smokers had higher
total cholesterol and triglyceride levels than
did nonsmokers (Table 2
).
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Arterial Compliance: SAC
Comparisons of mean values for indices of arterial
compliance are summarized in Table 3.
Mean SAC was significantly greater in the HRT group compared with the
non-HRT group (0.42±0.02 versus 0.34±0.02 U/mm Hg,
P=0.003). For the HRT group, there was no significant
difference in SAC for those receiving combined estrogen and progestin
therapy compared with those on estrogen alone (Table 3). Comparisons of
smokers with nonsmokers are shown in Table 4. Smokers on HRT had a higher mean SAC
than did smokers in the control group (0.41±0.02 versus 0.31±0.02
U/mm Hg, P=0.008). There was no significant difference
between smokers on HRT and control nonsmoking subjects (0.41±0.02
versus 0.35±0.03 U/mm Hg, P=NS).
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The best predictive multiple linear regression model was developed by incorporating systolic and diastolic BPs, pulse pressure, smoking status, cholesterol, triglycerides, BMI, heart rate, and alcohol intake status of all subjects. SAC correlated best with HRT status (P<0.0001, r=0.55). BMI (P=0.002), triglycerides (P=0.003), alcohol intake (P=0.02), and smoking status (P=0.04) were the only other significant correlates in the model. ANCOVA with BMI, triglycerides, alcohol intake, smoking status, and BP as covariates demonstrated that SAC was still significantly correlated with HRT status.
SAC decreased with age in both HRT and control groups. There was no
significant difference in the slope of the linear SAC-age relationship
between the HRT and control groups (Figure 3). However, at any given age, the HRT
group had a more favorable SAC than did controls, as
represented by a significant upward shift in the SAC-age
relationship. There was no correlation between duration of HRT use and
SAC.
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Carotid Compliance
Mean DC was not significantly different between the HRT and
non-HRT groups (Table 3). However, comparison of estrogen-alone with
estrogen-plus-progestin treatment subgroups showed significant
differences in mean DC, consistent with a greater degree of
arterial stiffness in the combined-therapy HRT group
compared with those on estrogen alone. In the smoking subgroup
analysis DC was higher in smokers on HRT
(44±4x10-3 versus
36±2x10-3/kPa, P=0.06) compared with
smokers in the control group. In nonsmokers mean DC was not
significantly different in the HRT and control groups (Table 4).
The best predictive multiple linear regression model, based on BP, age, HDL, LDL, triglycerides, smoking status, and HRT status of all subjects, demonstrated that DC was significantly correlated only with systolic BP (P<0.001).
Common Carotid Wall IMT
Mean arterial carotid wall IMT was 0.67±0.01 mm
in the HRT group compared with 0.74±0.02 mm in controls
(P<0.006). The mean IMT values for estrogen-treated and
combined estrogen and progestin–treated subgroups were not
significantly different (Table 3). Overall IMT was not significantly
different in smokers compared with nonsmokers (0.71±0.02 versus
0.69±0.02 mm); however, smokers on HRT had a significantly lower
IMT than did smokers not on HRT (0.65±0.01 versus 0.75±0.01 mm,
P=0.002) (Table 4). There was a significant increase in IMT
with age in both HRT and non-HRT groups. This IMT-age correlation was
stronger in the control group (r=0.51, P<0.001)
compared with the HRT group (r=0.32, P=0.04),
with the difference between linear regression lines slopes approaching
significance (P=0.08) (Figure 4). In subjects 
60 years of age IMT was
not significantly different in those on HRT compared with controls
(0.63±0.02 versus 0.66±0.02 mm, P=NS). In subjects
>60 years of age, those who were on HRT had a significantly lower mean
IMT (0.70±0.02 versus 0.80±0.03 mm, P=0.01).
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The best predictive multiple linear regression model for IMT was based on systolic and diastolic BPs, HRT status, age, alcohol intake, and activity levels of all subjects. IMT was significantly correlated with HRT status (P=0.002), systolic BP (P<0.0001), diastolic BP (P=0.004), and age (P=0.007). IMT was not significantly correlated with lipid levels. ANCOVA with BP and age as covariates demonstrated that IMT was still independently correlated with HRT status.
Relationships Between Arterial Compliance and Wall
Thickness
Linear regression analyses (Table 5) showed no significant relationship
between SAC and IMT for the HRT group (r=-0.13,
P=0.3) but a significant inverse correlation for the control
group (r=-0.31, P=0.006). DC was significantly
correlated with SAC in both HRT (r=0.40,
P<0.001) and control (r=0.38,
P=0.001) groups. DC was inversely correlated with IMT in
both HRT (r=-0.28, P=0.01) and control
(r=-0.35, P=0.001) groups.
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Discussion |
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Epidemiological evidence has strongly suggested that HRT may reduce the risk of cardiovascular disease in postmenopausal women.1 4 5 32 33 The results of long-term controlled trials such as the Women's Health Initiative study are not expected until early in the next century. Potential mechanisms for the effects of HRT on cardiovascular disease include alterations in plasma lipoproteins and lipid oxidation.5 7 8 These effects are estimated to account for
40% to 50% of the beneficial estrogen effect. Changes
in the coagulation pathways including
fibrinogen,34 modulation of the levels or effects
of vasoactive hormones,6 35 and changes in
arterial wall structure10 36 and
function37 38 39 40 41 42 have also been identified. The
results of the present study offer strong supporting evidence that
long-term estrogen therapy in postmenopausal women can beneficially
affect arterial structure and function. Indices of arterial structure and function can be measured accurately, reproducibly, and noninvasively by ultrasound. These measurements are well suited to clinical intervention trials to study surrogate clinical end points. IMT, as assessed by B-mode ultrasound imaging, provides an index of carotid wall structure and appears to be a useful marker of atherosclerosis. It is believed to measure the combined thickness of the intima and media,30 although Gamble et al31 reported that the measurement best represents total wall thickness. IMT has been correlated with the majority of cardiovascular risk factors, including age, male sex, hypertension, hypercholesterolemia, diabetes, and pack-years of smoking14 and also with the extent of coronary disease.15 IMT can also be influenced by antihypertensive43 44 and lipid-lowering45 46 therapy. In the present study IMT was significantly reduced by a mean value of 0.07 mm in the group of women on HRT compared with the age-matched control group. In the entire group of subjects, the multiple regression model revealed that IMT was significantly correlated with HRT status, age, and systolic and diastolic BP. IMT remained significantly correlated with HRT status after correction for age and BP. These results support the findings of the Asymptomatic Carotid Atherosclerosis Progression Study (ACAPS) investigators.36 Thus, HRT appears to produce changes in vessel wall structure over the long term, and this may be an important mechanism by which HRT exerts its cardiovascular protective effect. The mechanisms mediating HRT effects on arterial structure in postmenopausal women are not yet clarified. IMT may be influenced by lipid profile changes, but on available evidence, this is likely to account for only some of the variations between HRT and controls. Lipids were not correlated with IMT in this study.
SAC and common carotid compliance provide noninvasive measures of arterial function. They have been less studied when compared with IMT but are also affected by cardiovascular risk factors.17 18 22 SAC reflects the function of the proximal vascular system to convert pulsatile, systolic blood flow into continuous blood flow to the periphery. It is inversely proportional to arterial stiffness. In this study, mean SAC was higher in the HRT group and similar for combined HRT and estrogen-alone subgroups. These observations could not be explained by any differences between groups for weight, BMI, smoking status, alcohol intake, exercise levels. The HRT group had significantly lower total plasma cholesterol, LDL, and Lp(a) levels and higher HDL cholesterol levels. Thus, arterial compliance in the HRT group may have been influenced by changes in the vascular wall mediated by HRT-induced changes in plasma lipids or lipoprotein oxidation. This is unlikely to be the only mechanism, because SAC was not significantly correlated with lipid levels (except for triglycerides) in either the HRT or control group. ANCOVA, after adjustment for other all other significant correlates (BMI, smoking status, alcohol intake, plasma triglycerides, and BP), confirmed that SAC remained significantly correlated with HRT status.
Carotid arterial compliance measured by DC was similar in the HRT and non-HRT groups. Moreover, HRT status was not correlated with DC in a multiple regression model. Of interest was the observation that when compared with estrogen therapy alone, progestin addition to estrogen was associated with a significantly lower DC. It is perhaps surprising that SAC and DC were different in this respect. However, there are major differences between aortic and carotid artery structure. DC is also likely to be influenced by local endothelial and vessel wall factors or more distal cerebral vascular bed characteristics. Interactions between estrogen and progestin could occur at 1 or more of these sites.
A number of studies have now provided evidence of beneficial effects of estrogen therapy on arterial function. Pines et al38 used Doppler echocardiography to examine peak flow velocity, acceleration, and ejection times in postmenopausal women and observed that estrogen therapy increased both stroke volume and flow acceleration. Gangar et al39 reported an increase in the pulsatility index of the internal carotid artery in 12 postmenopausal women after 6 weeks of estradiol therapy. In a recent report from our group, Rajkumar and colleagues42 reported that SAC was highest in premenopausal women; in postmenopausal women, mean SAC was greater in HRT-treated compared with non-HRT–treated women. In a small group of postmenopausal women cessation of HRT for 4 weeks resulted in a significant fall in SAC.42 These data indicate that estrogen therapy has rapid-onset and -offset effects on arterial compliance. There is an increasing body of evidence suggesting that estrogen stimulates NO-mediated, endothelium-dependent vasodilatation.40 41 The influence of such endothelium-dependent changes may be an important contributing factor to the observed changes in arterial compliance in estrogen-treated subjects.
HRT prescription for women who smoke has long been controversial, primarily because of concerns over potential thrombosis risk (which remain to be substantiated). It would appear logical that smokers may receive benefit from HRT, given their increased risks of osteoporosis and heart disease. The results of the present study suggest that HRT confers greater benefits in smokers than in their nonsmoking counterparts. Moreover, indices of arterial function and structure in smokers were similar to those in nonsmoking controls, providing supporting evidence that smokers may derive significant benefit from HRT.
The structural composition of the arterial media is known to influence the compliance of an artery. In the present study, indices of function (SAC and DC) were significantly inversely correlated with IMT in the control group. However, the relationship between SAC and IMT was not significant in the HRT group. This apparent uncoupling of the arterial structure-function relationship in those on HRT suggests that long-term estrogen therapy may significantly alter that relationship. HRT-induced improvements in SAC are likely to be independent of arterial structural changes, given the relatively rapid onset of changes in arterial compliance and the apparent slowness of changes in IMT. It is quite feasible that in the long term, functional changes as a result of estrogen therapy may contribute to structural benefits in the arteries of postmenopausal women.
Recent data from the Atherosclerosis Risk in Communities (ARIC) study have demonstrated in a large group of subjects that an index of carotid arterial stiffness, after adjustment for age, height, diastolic diameter, and BP, did not increase with IMT except in those subjects with the greatest (top 10%) IMT measurements.47 These findings suggest that thick arteries are not necessarily stiff arteries. However, it is difficult to compare those results with those of the current study. In the ARIC study IMT was a composite measure from several carotid sites, while the index of carotid stiffness was a change in wall diameter derived from a mathematical model.
The effects of age on vascular parameters and the impact of
HRT on these age-related effects warrant discussion. Structural changes
have been demonstrated to occur slowly, consistent with the
natural history of atherosclerotic disease.48
Carotid wall IMT is lower in women than in men at all ages until the
mid 60s. Endogenous sex hormones, which persist into the
early postmenopausal years, are likely to play an important role in
cardiovascular protection. Interestingly, in the
current study the duration of HRT use was not associated with IMT even
after correction for age. In the ACAPS36 and
ARIC48 studies the reported annual rates of
progression of mean maximal carotid IMT for women aged 50 to 80 years
were 0.015 to 0.02 mm per year. In a preliminary report from
ACAPS, Espeland et al36 reported that HRT may
reduce or halt progression of IMT. Our results are in agreement with
theirs, since we observed a significantly lower mean IMT in the HRT
group compared with the control group. Moreover, the IMT-age
relationship appeared to be influenced by HRT, with the disparity
between controls and those on HRT increasing with age, because the
observed effects of HRT were more marked in older participants (Figure 4). This effect appears to be estrogen mediated because it is
apparently not compromised by concomitant progestin therapy. The
difference in IMT between the control and HRT groups was 0.07 mm,
consistent with at least a 4- to 5-year protective benefit of
HRT. Vascular function also deteriorates with age. Celemajer et
al40 reported an age-related reduction in
flow-mediated arterial dilatation, consistent with
attenuation of NO-mediated responsiveness. Our results show that
arterial function (ie, SAC and DC) deteriorated with age in
postmenopausal women. As previously discussed, functional changes have
been demonstrated to occur in the short term in response to
intervention with HRT.41 42 The observation that
HRT shifts the linear SAC-age relationship upward (Figure 3)
is consistent with these studies.
Overall, the findings of this cross-sectional study in a large group of women suggest an apparent protective effect of long-term estrogen therapy on age-related changes in arterial function and structure after menopause. These effects were evident in smokers and nonsmokers alike, with smokers on HRT having vascular indices that were similar to those of nonsmokers not on HRT. The HRT group exhibited the expected beneficial effects of therapy on plasma lipids; however, HRT status was a significant correlate of SAC and IMT after adjustment for lipid profiles. Long-term controlled trials are needed to further examine the impact of estrogen therapy on arterial structure and function in postmenopausal women and their relationship to cardiovascular end points.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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This study was supported by a grant-in-aid from the National Heart Foundation of Australia. We thank Dr N. Balazs and the Department of Clinical Biochemistry, Monash Medical Center, for the plasma lipid measurements. Robert Ziegenbein provided expert technical advice for the ultrasound measurements.
Received November 5, 1997; accepted February 5, 1998.
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References |
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