Heart disease in post menopausal women

ARRAY OF CARDIAC
DISEASES IN POST-
MENOPAUSAL WOMEN
Dr Vivek Baliga

Content
 Introduction
 CHD in Menopause
 SWAN Study
 Study 2
 HRT and heart diseases in post-menopausal
women
 Summary

Cardiac diseases in Post-menopausal
women
Introduction

Introduction
 Understanding the influence of the
menopausal transition on women’s risk of
coronary heart disease (CHD) remains
elusive.
 Women who experience early menopause,
especially due to surgical oophorectomy, are
at increased risk of CHD events compared
with age-matched pre-menopausal women.
Tunstall-Pedoe H. Myth and paradox of coronary risk and the menopause. Lancet
1998;351:1425–7.

Introduction
 Women’s rates of CHD do not increase
dramatically during perimenopause, but start
to climb exponentially in the post-menopausal
years.
 On the other hand, the post-menopausal
increase in CHD rates may reflect the
cumulative impact of earlier alterations in CHD
risk factors beginning during the menopausal
transition.
1998;351:1425–7.

CHD in Menopause
 Taken together, these disparate findings have
contributed to controversy about whether
menopause accelerates CHD risk or whether
increased CHD risk leads to earlier
menopause.
 One approach to understanding the
directionality of the effect is to evaluate
changes in risk factors for CHD during
perimenopause and early post-menopause.
1998;351:1425–7.

CHD in Menopause
 Epidemiological studies suggest that the
menopause is associated with increases in
total cholesterol and low-density lipoprotein
cholesterol (LDL-C), whereas increases in
blood pressure and weight during midlife are
more linear and appear to reflect chronological
aging.
 Many of the studies were also conducted
before the identification of emerging risk
factors, such as C-reactive protein (CRP) and
fibrinogen.Tunstall-Pedoe H. Myth and paradox of coronary risk and the menopause. Lancet
1998;351:1425–7.

SWAN study
Study of Women’s Health Across
the Nation

SWAN Study
 The aim is to describe the changes in a wide
array of risk factors, including
 lipids and lipoproteins,
 blood pressure,
 insulin, glucose, and
 hemostatic and inflammatory factors in women
before and after their final menstrual period
(FMP) and to ascertain whether changes in these
risk factors were related to ovarian aging or
chronological aging.
Sowers MF, Crawford S, Sternfeld B, et al. Design, survey sampling and recruitment methods of SWAN: a multi-center, multi-ethnic,
community-based cohort study of women and the menopausal transition. In: Wren J, Lobo RA, Kelsey J, Marcus R, editors.
Menopause: Biologyand Pathobiology. San Diego, CA: Academic Press, 2000:175–88.

SWAN Study
 The study sample was composed of 1,054
women who had their FMP by the end of 9
years of follow-up in SWAN (Study of
Women’s Health Across the Nation), a
longitudinal, multisite, community-based study
of 3,302 initially pre-menopausal and early
perimenopausal women.

SWAN Study
 Risk factors were selected for measurement in
the SWAN study if they were predictors of
CHD in women or if they were influenced by
ovarian hormones.
 All lipid and lipoprotein fractions were
analyzed on ethylenediamine tetraacetic acid
treated plasma.

SWAN Study
 Total cholesterol and triglycerides were
analyzed by enzymatic methods and high-
density lipoprotein cholesterol (HDL-C) was
isolated using heparin-2M manganese
chloride.

Age- adjusted baseline
characteristics

CHD in Menopause
 The mean adjusted changes across time in
total cholesterol, LDL-C, apolipoprotein (Apo)
B, HDL-C, and Apo A-I were fit better by the
piecewise linear model than by the linear
model.
 The increases in total cholesterol, LDL-C, and
Apo B were substantial around the FMP and
were significantly greater than the increases in
total cholesterol, LDL-C, and Apo B before and
after the FMP interval.

Lipids Annual and Estimated
Means
Pattern of low-density lipoprotein cholesterol (LDL-C) (A), apolipoprotein (Apo) B (B), high-density lipoprotein
cholesterol (HDL-C) (C), and Apo A-I (D) across the SWAN study follow-up period showing the annual covariate
adjusted mean values compared with estimated values by the better fitting piecewise linear model (menopause
related); relative Akaike information criterion fit for the piecewise linear versus linear models, 1.0430 (95% CI:
1.0130 to 1.0730), 1.0340 (95% CI: 1.0092 to 1.0588), 1.0486 (95% CI: 1.0203 to 1.0769), and 1.0255 (95% CI:
1.0036 to 1.0474), respectivelyBittner V. Menopause and cardiovascular risk: cause or consequence? J Am Coll Cardiol 2006;47:1984–6.

Segment- specific slope for
cardiovascular risk factors
Cardiovascular risk factors Where Piecewise Linear Trajectory Fits Better Than
Linear Trajectory (Relative Fit >1)
Bittner V. Menopause and cardiovascular risk: cause or consequence? J Am Coll Cardiol 2006;47:1984–6.

CHD in Menopause
 Effect modification by baseline weight was
statistically significant for total cholesterol and
LDL-C and Apo B, largely due to a flattening of
lipids in heavier women after the FMP.
 The steep upward incline around the FMP
occurred in all 3 weight tertiles.

Lipid Annual Means According to
Baseline Weight
Pattern of total cholesterol (A), LDL-C (B), and Apo B (C) across the SWAN study follow-up period showing the
annual covariate adjusted mean values in women categorized by baseline weight tertiles. Slopes around the FMP
interval were identical in the 3 groups for total cholesterol, LDL-C, and Apo B (p values 0.28, respectively),
whereas slopes more than 1 year after the FMP differed (p values 0.01, respectively). FMP final menstrual period

CHD in Menopause
 Linear models provided a better fit than did
piecewise models for the changes across time
in glucose, t-PA-ag, PAI-1, and fibrinogen,
relative AIC fits 1.
 Linear and piecewise models were of
equivalent fit for systolic and diastolic blood
pressure, Lp(a), insulin, factor VIIc, and CRP
trajectories, relative AIC fits included 1.

CHD in Menopause
 The aims of the study were to evaluate the
change in CHD risk factors in relation to the FMP,
independent of age and other confounders,
among women who experienced a natural
menopause and to examine the extent of ethnic
differences in those patterns.
 The results showed significant increases in total
cholesterol, LDL-C, and Apo B within a year of the
FMP, relative to the observed increase over time
intervals before or after.

CHD in Menopause
 These FMP-related increases were similar in
women classified into tertiles by baseline
weight.
 Importantly, the rate of change relative to FMP
did not vary by ethnicity, suggesting that
menopause had a uniform influence on lipids.

CHD in Menopause
 The influence of the interval surrounding the FMP
on total cholesterol, LDL-C, and Apo B was
independent of age as well as the many
covariates that vary by ethnicity, including weight,
weight gain, and medications.
 The present analysis is the first to document the
effects of the natural menopausal transition
anchored prospectively by the FMP with sufficient
follow-up, annual assessment of risk factors,
accurate and detailed timing of menopause, and
extensive covariate adjustment.

CHD in Menopause
 These findings are consistent with the
hypothesis that the increase in CHD in post-
menopausal women may in part be related to
the earlier changes in lipids associated with
the menopausal transition.
 The analyses showed no influence of the FMP
on blood pressure, insulin, glucose, Lp(a), and
hemostatic and inflammatory factors.

CHD in Menopause
 These findings have potential clinical implications
because identification of modifiable risk factors
and early intervention may reduce women’s
increased risk of CHD after menopause.
 Although an increase in LDL-C and a decrease in
HDL-C between pre-menopause and post-
menopause have been previously reported in
healthy Caucasian women, this data specifically
identify the critical time period, the year
immediately around the FMP, as the time of the
most adverse changes in the lipid profile in all
ethnic groups.

CHD in Menopause
 Although absolute levels of LDL-C were within
what is considered the normal range, even lipids
in the normal range during the pre-menopausal
and perimenopausal transition predict later
coronary calcification and carotid intima media
thickness.
 Whether the threshold levels for lipid-lowering
therapy should change around the time of
menopause or whether the absolute or relative
degree of change in lipids (independent of
premenopausal levels) predicts future CHD
events merits further study.Bittner V. Menopause and cardiovascular risk: cause or consequence? J Am Coll Cardiol 2006;47:1984–6.

CHD in Menopause
 The menopause-associated changes in total
cholesterol, LDL-C, and Apo B observed here
may play an important role in women’s
increased risk of CHD in the post-menopausal
years.

Study 2
 The aims of the present study, were to
examine the relationships among plasma lipids
and apoB and the sex hormones, cortisol,
insulin and certain cytokines in selected
groups of overweight Turkish postmenopausal
women.
Altan ONAT et al. Evidence for a complex risk profile in obese postmenopausal Turkish women with
hypertriglyceridaemia and elevated apolipoprotein B. Clinical Science (2004) 107, 97–104

Study 2
 The hypothesis was that hypertriglyceridaemia
with elevated apoB would be associated with a
more androgenic hormonal pattern.
 They also tested the hypothesis that apoB
would be associated with a wider array of risk
factors than with LDL-C.

Levels of risk factors and risk score in
three groups of obese postmenopausal
women

Levels of plasma sex hormones in
obese groups of women

Spearman correlation coefficients (r)
among risk parameters and hormone
values in 178 women

Study 2
 The relationship of the sex hormones with
obesity and dyslipidaemia is complex and
remains incompletely understood.
 Plasma levels of SHBG are inversely
associated with BMI, and an obesity-induced
fall in SHBG results in an increased turnover
of androgens.

Study 2
 The data in the present study do not establish
the pathophysiological basis for the clustering
of risk factors in obese post menopausal
Turkish women with hypertriglyceridaemia with
elevated apoB.
 Clearly, it is not simply obesity that is
responsible, because BMI was the same in all
three groups.

Study 2
 In summary, hypertriglyceridaemia with
elevated apoB is an important proatherogenic
dyslipoproteinaemia in obese post
menopausal Turkish women.

HRT and heart diseases in post-
menopausal women
 In numerous observational studies,
postmenopausal women taking ERT/ HRT
have been shown to have a 3 0-50% lower risk
of heart disease than do nonusers of
hormones.
 Inmost studies, investigators have reported on
ERT use but, more recently, similar reductions
in cardiovascular risk have been found for
HRT, as well.
Matthews KA, Meilahn E, Kuller LH, Kelsehy SF, Caggiula AW, Wing RR. Menopause and risk factors for coronary heart disease. N
Engl J Med 1989;321:641– 6.

menopausal women
 Because heart disease is the major cause of
death and disability among women in many
developed countries, the question of whether
postmenopausal hormone therapy prevents
heart disease is an important one; if protection
is afforded, ERT/ HRT use could potentially
benefit millions of women.
Engl J Med 1989;321:641– 6.

menopausal women
 Despite the abundant evidence for cardiovascular
benefit, however, it is the opinion that estrogen
therapy should not currently be prescribed for the
purpose of heart disease prevention, for the
following reasons.
 No randomized clinical trials of ERT/ HRT and primary
prevention of heart disease have been completed.
 No benefit of hormone therapy for secondary
prevention of recurrent clinical events or of
atherosclerosis progression among women with
clinically diagnosed heart disease was shown in the
two randomized clinical trials completed to date.
Engl J Med 1989;321:641– 6.

Summary
 Women who experience early menopause,
especially due to surgical oophorectomy, are
at increased risk of CHD events compared
with age-matched pre-menopausal women.
 Women experience a unique increase in lipids
at the time of the FMP.
 Monitoring lipids in perimenopausal women
should enhance primary prevention of CHD.

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Heart disease in post menopausal women

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