nfralick
Sun, 10/30/2022 - 23:11
Edited Text
PostmenopausaI estrogen therapy
and cardiovascular disease in
women / by Kristine A. Komosa.
Thesis Nurs. 2900 K81p c.2
POSTMENOPAUSAL ESTROGEN THERAPY AND
CARDIOVASCULAR DISEASE IN WOMEN
By
Kristine A. Komosa RN, BSN
Submitted in Partial Fulfillment of the Requirements for
the Master of Science in Nursing Degree
Edinboro University of Pennsylvania
Approved by:
Jpuith Schilling, CRNP, PhD
Committee Chairperson
Date
2
Vd
Jo [?h Or. Cacchione, MD, FACC
mittee Member
Date
Dorothy \Stano Carlson, RN, DEd
Committee Member
Date
< ,^3
Abstract
Postmenopausal Estrogen Replacement Therapy and Cardiovascular Disease
in Women
The purpose of this study was to analyze the relationship between
postmenopausal estrogen therapy and the presence of coronary artery disease
(CAD), giving consideration to the other coexisting CAD risk factors of
obesity, smoking, hypertension, diabetes mellitus, and CAD history. A
retrospective descriptive research design was utilized. Data were collected
using a researcher-designed survey that included subject interview and
medical record review. The sample of 36 postmenopausal women was
classified into 3 groups according to estrogen use: current users (n=9), past
users (n=5), and those who had never used estrogen (n=22). The data were
analyzed using descriptive and inferential statistics and nonparametric tests.
A p=0.05 level of significance was used. A Fisher’s exact test showed no
statistically significant differences among the estrogen groups in the
presence of CAD or presence of obesity, smoking, hypertension, diabetes
mellitus, and CAD history. A Cramer’s V was used for analysis of
relationships in the study. A low positive correlation (PH).26) was found
between estrogen use and the presence of CAD, however this was not
statistically significant. A strong positive relationship (r=1.00) was found
'i
between history of CAD and presence of CAD in past users of estrogen
(n=5), which was significant at p=0.03. The benefit of estrogen therapy as a
means of CAD prevention in postmenopausal women cannot be inferred
from the results of this study.
Acknowledgements
I would like to take this opportunity to recognize the efforts of the
individuals who contributed to the development of this thesis. First, I would
like to acknowledge the committee members: Dr. Judith Schilling, for her
time as committee chair, Dr. Joseph Cacchione, for his clinical expertise,
and Dr. Dorothy Carlson, for her assistance and expertise with data analysis,
I have learned much from all of them. I would also like to recognize the
efforts of my coworkers, particularly Mike Ochalek, Cara Milani, Dana
Webb, and Linda Scanlon, their assistance with data collection was greatly
appreciated. Finally, I would like to thank my husband and family for their
patience and support throughout these months.
Ur
Table of Contents
Page
Abstract
ii
Acknowledgements
iv
List of Tables
ix
Chapter 1: Introduction
1
Background of the Problem
1
Statement of the Problem
3
Theoretical Framework
3
Self-Care
4
Self-Care Agency
5
Therapeutic Self-Care Demand
6
Self-Care Deficit
6
Nursing Agency
7
Nursing System
8
Statement of Purpose
8
Assumptions
9
Limitations
9
Definition of Terms
10
Summary.
12
Chapter 2 : Review of Literature
Cardiovascular Disease in Women
14
14
Mortality
14
Morbidity
15
Risk Factors
16
Menopause
17
Physiologic Consequences
18
Methods of Hormone Therapy
18
Role of Estrogen in the Prevention of CAD
20
Mechanisms of Action
22
Primary Prevention
24
Secondary Prevention
26
Summary
27
Chapter 3: Methodology
29
Hypothesis
29
Operational Definitions
29
Setting
31
Sample
31
Pilot Study
32
Research Design
33
Instrumentation..
34
Inter-rater Reliability
35
Procedure..
36
Protection of Human Rights
37
Data Analysis
37
Summary
40
Chapter 4: Results
41
Tests of Independence
41
Presence of CAD
42
Obesity
42
Smoking
43
Hypertension
44
Diabetes
45
History of CAD
45
Relationship and Trend Analysis
46
Current Estrogen Users
47
Past Estrogen Users
48
Never Estrogen Users
51
Summary
Chapter 5: Discussion....
writ
Conclusions
57
Recommendations for Future Research
59
Summary
60
References
61
Appendices
66
A. CAD and the Role of Estrogen Survey
67
B. Case Study
68
C. Steps to Obtain Informed Consent
69
D. Signed Application to Conduct Research
70
E. Institutional Review Board Letter
71
List of Tables
Table
Page
1. Estrogen Use and Presence of CAD
42
2. Estrogen Use and Obesity
43
3. Estrogen Use and Smoking
44
4. Estrogen Use and Hypertension
45
5. Estrogen Use and Diabetes
46
6. Estrogen Use and History of CAD
47
7. Risk Factors and Presence of CAD in Current Users of Estrogen
49
8. Risk Factors and Presence of CAD in Past Users of Estrogen
50
9. Risk Factors and Presence of Cad in Never Users of Estrogen
52
1
Chapter 1
Introduction
This chapter provides an overview of the problem of coronary artery
disease (CAD) in women and the role of estrogen therapy in its prevention.
Dorthea Orem’s (1995) Theory of Self-Care was used as the theoretical
framework for this study. The background of the problem and the statement
of the problem are addressed within this chapter. This chapter also considers
assumptions and limitations of the study, and provides a definition of terms;
Background of the Problem
Cardiovascular disease (CVD) is the leading killer of women, claiming
more than 500,000 American lives per year (American Heart Association
[AHA], 1999). CVD accounts for one in every two women’s deaths, in
comparison to the one in 27 deaths from breast cancer (AHA, 1999). Women
generally develop CVD 10 years later than their male counterparts, with an
average age of 72.5 years at diagnosis, in comparison to the age of 62.8 years
in men (AHA). The cardioprotective effects of estrogen are thought to play a
role in this age difference.
In 1992, the National Heart, Lung and Blood Institute held an
invitational conference entitled “Cardiovascular Health and Disease in
Women” (Wenger, Speroff, & Packard, 1993). The purpose of this conference
2
was to identify gaps in current knowledge about CVD in women in order to
improve the outcome of care. Some of the largest gaps in cardiovascular care
of women included evaluation and treatment, as well as prognosis (Wenger et
al.). Differences between men and women in the of treatment of CVD and
outcomes were identified:
1. Although women experience greater functional limitations due to
chest pain than men, they undergo intensive and invasive evaluation (such as
cardiac angiography) less frequently than men.
2. Women are less likely to be eligible for thrombolytic therapy
following myocardial infarction than men due to a later hospital presentation,
advanced age, and greater comorbid conditions.
3. Women who undergo coronary artery bypass grafting are usually
sicker at the time of surgery, are at a more advanced stage of illness, and
require surgery on a greater emergent basis than men.
4. Women have an overall worse prognosis than men following
myocardial infarction, even with the use of thrombolytics.
5. Women are also likely to have worse outcomes following
percutaneous transluminal coronary angioplasty (PTCA) or coronary artery
bypass grafting.
3
Estrogen has been shown to have a protective effect in the prevention
of cardiovascular disease in women, reducing risk by approximately 50%
(Nabulsi et al., 1993). Mechanisms include: (a) alteration of serum lipid
levels, with increased high density lipoprotein cholesterol (HDL-C) and
decreased low density lipoprotein cholesterol (LDL-C) in estrogen users, (b)
alteration of hemostatic factors such as fibrinogen, with decreased fibrinogen
levels in estrogen users, and (c) alterations of serum glucose and insulin, with
decreased fasting glucose and insulin in estrogen users (Nabulsi et al.).
Statement of the Problem
Cardiovascular disease is the number one cause of death in women,
carrying a higher mortality rate in women than men (AHA, 1999). Despite
this fact, women undergo less invasive and intense evaluation for this disease,
with poorer outcomes of treatment than men (Wenger et al., 1993). The use of
postmenopausal estrogen has been shown to reduce the risk of cardiovascular
disease in women (Nabulsi et al., 1993). Further research into the relationship
between estrogen and the development of cardiovascular disease has been
recommended (Wenger et al.).
Theoretical Framework
The theoretical framework used for this study was Dorthea Orem’s
Self-care Deficit Theory (Orem, 1995). Orem’s theory includes six core
4
concepts, linked by three interrelated theories. These concepts are related to
this research study and have implications for both the postmenopausal woman
or the nurse practitioner.
Orem s Self-Care Theory is comprised of three interrelated theories: (a)
theory of self-care, (b) theory of self-care deficit, (c) theory of nursing system
(Hartweg, 1991). These six core concepts are self-care, self-care agency,
therapeutic self-care demand, self-care deficit, nursing agency, and nursing
system. Orem (1995) also includes the peripheral concept of basic
conditioning factors, which influence certain patient and nursing ideas.
Self-Care. Self-care is defined by Orem (1995) as “the practice of
activities that individuals initiate and perform on their own behalf in
maintaining life, health, and well-being” (p. 117). For an individual to
perform a self-care action, he or she must have knowledge of this action and
its relation to health and well-being (Hartweg, 1991). The self-care action
must then be deliberately performed with a particular health goal in mind.
In relation to this study, the health goal is the prevention of coronary
artery disease in postmenopausal women. The risk of coronary artery disease
can be decreased with estrogen therapy (Grodstein et al., 1996). The self-care
action of the postmenopausal woman would be to acquire the information
needed to make a decision regarding estrogen therapy. In order to do this, she
5
must understand the increased risk of cardiovascular disease following
menopause in order to make a deliberate decision regarding the use of
estrogen therapy.
Self-care Agency. The second concept in Orem’s theory is the concept
of self-care agency, which is defined as the ability of an individual to engage
in self-care activity. These abilities are arranged in a hierarchical structure
with basic functional ability at the base, followed by power components such
as motivation and reasoning, and with the ability to determine the appropriate
actions and integrate them into daily routine at the top of the structure
(Hartweg, 1991). Basic conditioning factors that relate to this concept include
the individual’s age, gender, developmental stage, cultural background,
family, pattern of living, and environment (Hartweg).
In following Orem’s model, the postmenopausal woman would obtain
information regarding her risk of cardiovascular disease and make an
informed decision regarding the use of estrogen therapy. A conditioning
factor influencing her decision may be that a family member taking estrogen
developed breast cancer. She may strongly believe that this may happen to
her. Another conditioning factor may be her educational level. If she has a
below average reading level, she may not be able to comprehend available
6
literature. If she decided to begin estrogen therapy, she would then integrate
this into her daily lifestyle.
Therapeutic Self-care Demand. The third concept in Orem’s theory is
therapeutic self-care demand, which can be defined as all the self-care actions
that should be performed by an individual over time to maintain health. These
actions are also referred to as self-care requisites, which are divided into
universal requisites, developmental requisites, and health deviation self-care
requisites (Orem, 1995).
This study will address postmenopausal estrogen therapy as a health
deviation self-care requisite. Orem (1995) wrote that a health deviation self-
care requisite is something that either prevents further deviations due to a
present condition, or controls an existing deviation. In this study, menopause
is the existing condition that has a further deviation of coronary artery disease
in the absence of estrogen therapy. This study concerned the role of estrogen
as a health care deviation requisite of the postmenopausal woman.
Self-care-Deficit. The fourth concept of Orem s theory is self-care
deficit, which is the relationship between self-care agency and therapeutic
self-care demand (Orem, 1995). This relationship may show self-care agency
as greater than therapeutic self-care demand (TSCD), less than TSCD, or
equal to TSCD. Orem stresses that self-care deficit is not a disorder but an
7
expression of the relationship between these two concepts. A self-care deficit
must exist for the role of nursing to be legitimate (Hartweg, 1991).
In applymg the concept of self-care deficit to this study, a deficit would
occur in a postmenopausal woman who is not taking estrogen therapy and is
unaware of the cardiovascular risks. This would demonstrate a legitimate
need for the services of a nurse practitioner who would educate the woman
concerning the risks and benefits of estrogen therapy, prescribe the
appropriate therapy, and educate the woman on how to integrate this therapy
into her daily routine.
Nursing Agency. The fifth concept in Orem’s theory is nursing agency,
which is defined as the ability of the nurse to identify an individual’s self-care
requisites and to assist this individual in meeting these requisites (Orem,
1995). This ability has a base in the sciences, humanities, and nursing
experience over time, and vanes with individual nurses according to their
respective experiences and practice areas. Basic conditioning factors are also
applicable to this concept, in that the nurse’s age, developmental level,
cultural background, and environment will influence the way that he/she
addresses the patient’s self-care requisites (Hartweg, 1991).
In this study, nursing agency involves the knowledge base of the nurse
practitioner regarding the relationship of estrogen therapy and cardiovascular
8
risk. The implications of this study will add to the knowledge base and serve
to provide additional evidence regarding estrogen in relation to coronary
artery disease.
Nursing System. The sixth concept in Orem’s theory is nursing system,
defined as the actions and interactions between nurses and patients in nursing
practice. Nursing systems are divided into three separate systems, (a) the
wholly compensatory system in which the nurse performs all self-care for the
patient, (b) the partly compensatory system in which the nurse and the patient
share self-care responsibility, (c) the supportive-educative system in which
the patient is responsible for his/her own self-care and the nurse provides
guidance and education regarding self-care activity (Orem, 1995). Utilizing
information from this study, the nurse practitioner functions in the
supportive/educative system, providing information to postmenopausal
patients regarding the cardiovascular benefit of estrogen therapy.
Statement of Purpose
It has been recommended in the literature that further research into the
relationship between postmenopausal estrogen therapy and cardiovascular
disease be conducted (Wenger et al., 1993). The purpose of this current study
was to analyze the relationship between estrogen therapy and presence of
CAD in postmenopausal women undergoing cardiac angiography.
9
Consideration was given to the coexisting cardiovascular risk factors of
smoking, obesity, hypertension, diabetes mellitus, and prior history of CAD.
Assumptions
The assumptions of this study were as follows:
• ■ The onset of cardiovascular disease can be delayed or prevented with
estrogen therapy.
2. The women being studied are postmenopausal.
3. The women being studied know whether or not they have been
taking estrogen therapy.
4. Cardiac angiography results were accurately documented in the
patients’ charts.
5. Survey data were obtained in a consistent manner.
Limitations
The limitations of this study were as follows:
1. The sample studied was from the population of a cardiac
catheterization laboratory and, therefore, a higher incidence of cardiovascular
disease may be present in comparison to the general population.
2. The study was performed retrospectively and, therefore, the accuracy
of the study data will depend upon the accuracy of the initial documentation.
10
3. Only subjects receiving treatment for hypertension were classified as
being hypertensive in this study and, therefore, undiagnosed hypertensive
subjects were not accounted for in this study.
4. Only subjects receiving treatment for diabetes mellitus were
classified as diabetic in this study and, therefore, undiagnosed diabetics were
not accounted for in this study.
5. Results of this study were limited to patients within one hospital
cardiac catheterization laboratory and, therefore, they may not be
generalizable to other populations.
6. This study did not account for other independent risk factors for
CAD that may be present such as homocystinemia, elevated lipoprotein (a), or
elevated apolipoprotein B.
Definition of Terms
The terms used in this study were as follows:
1 Cardiac angiography involves the injection of a contrast agent into
the ostia of either the left main or right coronary arteries in order to determine
the percentage of coronary artery narrowing at a site of obstruction, if any
(Barry, 1996).
2. Cardiovascular disease (CVD) is a general diagnostic category that
consists of several disease entities affecting the cardiovascular system.
11
Included in this category are coronary artery disease, peripheral vascular
disease, and structural heart dise:ase (Friedewald, 1996).
3. Coronary artery disease (CAD), a form of cardiovascular disease, is
arteriosclerosis of the coronary arteries that involves the formation of lipid-
rich, thickened, and hardened lesions on the interior coronary artery wall.
These lesions may rupture or become large enough to obstruct the entire
artery lumen, leading to tissue ischemia and necrosis, clinically seen as
myocardial infarction (Ross, 1996). Risk factors for the development of CAD
include hyperlipidemia, decreased HDL-C level, smoking, diabetes mellitus,
hypertension, obesity, physical inactivity, and genetic predisposition (Ross,
1996).
4. Hormone therapy (HT) is defined as noncontraceptive estrogen use
during the menopause (Greendale & Judd, 1995). Estrogen may be
administered in one of two ways: (a) unopposed, in which only estrogen is
given in either oral or transdermal form, or (b) given with progestin on a daily
or cyclic basis (Greendale & Judd).
5. Hyperlipidemia is defined as an abnormally elevated total serum
cholesterol and/or triglyceride levels (Witzum & Steinberg, 1996). The total
cholesterol is divided into high density lipoprotein (HDL-C), which serves to
remove excess cholesterol and decrease lipid deposits on arterial walls, and
12
low density lipoprotein (LDL-C), which deposits on arterial walls leading to
atheroma formation (Witzum & Steinberg).
6. Menopause is the cessation of ovarian function that leads to
permanent amenorrhea, occurring at an average age of 50 years (Greendale &
Judd, 1995).
Summary
Cardiovascular disease (CVD) is the leading cause of mortality in
women (AHA, 1999). Although the prevalence of CVD is higher in men,
women are more likely to die from CVD than men (AHA). Gaps in the
diagnosis and treatment of CVD in women have been identified which
contribute to the poorer prognosis in women (Wenger et al., 1993). Women
have also been underrepresented in research regarding CVD, leading to
insufficient information concerning prevention, diagnosis, and treatment of
CVD in women (Wenger et al., 1993). Estrogen has been shown to have a
cardioprotective effect in the development of CVD in women, with further
research into this area being recommended (Nabulsi et al., 1993).
The purpose of this study was to perform a retrospective analysis of
estrogen use in postmenopausal women over 50 years of age with
angiographic evidence of CAD. Assumptions and limitations of this study
13
were expressed and definitions of the terms used within the study were
provided.
The theoretical framework used for this study was Dorthea Orem’s
Self-Care Theory. Estrogen therapy was identified as a health deviation self-
care requisite of the postmenopausal woman. This was followed by a
discussion of the role of the nurse practitioner within a supportive-educative
nursing system.
14
Chapter 2
Review of Literature
This chapter provides a review of the current literature concerning the
role of hormone therapy in the prevention of cardiovascular disease (CVD).
The differences in morbidity, mortality, and risk factor development
between men and women are discussed. The physiologic consequences of
menopause, means of hormone therapy, and the role of hormone therapy as
primary and secondary prevention for CVD are reviewed.
Cardiovascular Disease in Women
Cardiovascular disease is a major public health concern in older
women, with costs of CVD and stroke in both men and women exceeding
$250 billion in 1997 (AHA, 1999). Although mortality rates for CVD have
decreased over the past few decades, the rate of decline is less for women
than men (Mosca et al., 1997). CVD has reached an epidemic status in
women. It ranks first among all disease categories of hospital discharges for
women (Mosca et al.), with 2.5 million women being hospitalized each year
for CVD (Wenger et al., 1993).
Mortality. Cardiovascular disease is the leading killer of women m the
United States, claiming 500,000 lives per year (AHA, 1999). One out of
every two women’s deaths is from CVD, a stark comparison to the one out
15
of 27 for breast cancer. A disconcerting finding of the Framingham Heart
Study was that two-thirds of the sudden deaths due to CVD in women
occurred in women having no symptoms of disease (Mosca et al.).
Ethnic differences in CVD deaths have also been identified (Mosca et
al., 1997). Although the overall death rates for CVD are higher in blacks than
whites, black women have a 34% higher mortality rate than white women; in
comparison, black men have only a 5% higher death rate than white men.
Mortality rates for CVD are lower in Mexican-American men than white
men, however, there is no mortality difference between Mexican-American
women and white women.
An unequal gender mortality rate is also observed with
revascularization procedures following myocardial infarction (Mosca et al.,
1997). The Global Utilization of Streptokinase and TPA for Occluded
Arteries (GUSTO-1) study showed the 30-day mortality rate in women to be
double that of men (Mosca et al.). With regard to percutaneous transluminal
coronary angioplasty (PTCA), the long term prognosis was equal in women
and men, however, intraprocedural mortality was three times higher in
women.
Morbidity. A number of factors affecting morbidity from CVD have
been identified (Wenger et al., 1993). It has been shown that women
16
undergo less aggressive and intensive evaluation for CVD than men, leading
to fewer revascularization procedures such as PTCA and coronary artery
bypass grafting. Women who undergo these procedures are typically at a
more advanced stage of disease. Additionally, women have smaller coronary
artery size than men, which further complicates revascularization procedures
(Wenger et al.). The presentation of women with MI differs from men, with
women being more likely to have atypical symptoms such as epigastric pain,
nausea, and fatigue than men (Mosca et al., 1997).
Risk factors. The risk factors for CVD are similar for both women and
men (Mosca et al., 1997). However, certain gender differences regarding
some of these risk factors have been identified (Mosca et al.). Following is a
discussion of these risk factors and how they differ for women.
1. Smoking is the leading preventable cause for CVD, producing a
two to four-fold elevation in risk for both women and men. In the United
States, an overall decline in cigarette smoking has been observed, however,
the rate of smoking cessation in women has shown a slower decline than in
men.
2. Elevated total serum cholesterol and LDL-C are risk factors for
both women and men. Decreased HDL-C has also been shown to be a
17
predictor of CVD morbidity and mortality for both sexes, however, it has
been found to be a stronger predictor for women than men.
3. Both systolic and diastolic hypertension have been found to have a
strong association with CVD in men and women. Isolated systolic
hypertension is of particular concern in elderly women, with a prevalence of
30% in women over 65 years of age.
4. Persons with Type 1 or Type 2 diabetes have a two-fold higher
incidence of myocardial infarction in comparison to nondiabetics, with
diabetic women developing ischemic heart disease at a higher rate than
diabetic men (Ross, 1996). A contributing factor to this increase in risk is the
pattern of low HDL cholesterol, high triglycerides, and insulin resistance
seen in those with diabetes (Sacks, 1995).
5. Data from the Framingham Heart Study gave evidence of a higher
rate of recurrent infarction and heart failure in women following MI
(Wenger, 1995). In the Framingham study, reinfarction following MI
occurred within the first year in 40% of women, in comparison to 13 /o of
men.
Menopause
Menopause can be defined as the cessation of ovarian function which
leads to permanent amenorrhea (Greendale & Judd, 1995). Twelve months
18
of amenorrhea is a significant indicator of the cessation of ovarian function.
The average age of menopause is 50 years (Greendale & Judd). Following
is
a discussion of the physiologic consequences of menopause for the
cardiovascular system, as well as a discussion of the methods of hormone
therapy.
Physiologic consequences. The most profound physiologic
consequence of menopause is upon serum lipid levels, with the average total
cholesterol level in postmenopausal women exceeding the average total
cholesterol level in men (Murabito, 1995). Postmenopausal women have
been found to have higher total cholesterol, LDL cholesterol, and
triglyceride levels than their premenopausal counterparts (Matthews et al.,
1989). In terms of cholesterol, HDL-C is the strongest predictor of CVD
risk, postmenopausal women have been found to have significantly lower
levels of HDL-C in comparison to premenopausal women (Matthews et al.,
1989).
Method of hormone therapy, Estrogen therapy is defined as
noncontraceptive estrogen use in the menopause (Greendale & Judd, 1995).
There are primarily two methods of estrogen therapy, (a) unopposed, which
is estrogen given alone on a daily basis, and (b) estrogen with progestin,
given as a fixed daily dose or on a cyclic basis (Greendale & Judd). The
19
following is a discussion of each method and the risks and advantages of
each.
Administering estrogen on a continuous or cyclic basis, is a method
referred to as unopposed estrogen therapy (Greendale & Judd, 1995). This
method of treatment is preferred for women without an intact uterus, since
estrogen alone confers a high risk of endometrial hyperplasia (Greendale &
Judd). Women with an intact uterus who develop intolerable side effects to
progestin may also be considered for this type of therapy, however,
surveillance biopsies may be required in order to monitor for the
development of endometrial hyperplasia (Greendale & Judd). The most
commonly prescribed form of estrogen in the United States is conjugated
equine estrogen (CEE) at a dose of 0.625mg per day (Greendale & Judd).
Transdermal preparations are available as well, with comparable
effectiveness in menopausal symptom relief and osteoporosis prevention.
The effectiveness of transdermal estrogen as compared to oral therapy in the
prevention of cardiovascular disease has not been demonstrated at this time
(Greendale & Judd).
Combination therapy with CEE 0.625mg and medroxyprogesterone
2.5mg to 5mg administered daily or on a cyclic basis is the next method of
hormone therapy (Greendale & Judd, 1995). This is the therapy of choice for
20
women with an intact uterus as it reduces the risk of endometrial
hyperplasia. Progesterone confers no additional benefit in women without a
uterus (Greendale & Judd). Continuous regimens may be preferred by some
women m that they minimize the undesirable side effects associated with
progestins such as headache, bloating, cramping, and vaginal bleeding
(Greendale & Judd).
Role of Estrogen in the Prevention of CVD
The relationship between menopause, estrogen, and CVD has been a
subject of interest since the early decades of this century (Barrett-Connor &
Bush, 1991). The earliest studies in the 1930s observed differences in the
prevalence of CVD between older and younger subjects, followed by animal
experiments studying the relationship between estrogen and atherosclerosis
(Barrett-Connor & Bush). It has been observed in the literature that CVD
risk is substantially reduced in estrogen users, who have a 50% lower risk
than nonusers (Barrett-Connor & Bush). However, this statement is not
without controversy, with conflicting results being noted in the Framingham
Heart Study, which has shown a statistically significant increase in CVD
mortality among estrogen users (Wilson et al., 1985). Another source of
controversy is the criticism that observational studies of estrogen and CVD
are subject to a certain amount of selection bias (Matthews et al., 1995). A
21
study was performed by Matthews et al. in order to determine if
postmenopausal women being recommended for hormone therapy had a
better cardiovascular risk profile than nonusers. The study included an initial
sample of 541 premenopausal women who were evaluated for
cardiovascular risk factors and psychosocial factors. After an 8 year period,
355 of these women had become postmenopausal, and 157 of them reported
estrogen use. The premenopausal characteristics between users of estrogen
therapy and nonusers were then compared. The results showed that estrogen
users were better educated; had higher levels of HDL-C, physical activity
and alcohol use; and had lower levels of LDL-C, systolic and diastolic blood
pressure, and weight than nonusers (Matthews et al.).
The role of estrogen and CVD prevention continues to be a strong
topic of interest, with continuing research into the employment of estrogen
as a means of both primary and secondary prevention in low and high risk
individuals (Barrett-Connor & Bush, 1991). Also of interest are the
differences in the reduction of CVD risk factors between unopposed
estrogen regimens and combination estrogen/progestin regimens (Barrett-
Connor & Bush). Current studies regarding estrogen’s mechanisms of action
and its role as a primary and secondary prevention agent, as well as studies
22
regarding the differences between unopposed estrogen and
estrogen/progestin regimens, will be discussed next.
Mechanisms of action.. The effects of estrogen upon serum lipid levels
has been the most promising finding in the literature. Research into the
effects upon other CVD risks such as hemostatic factors, carbohydrate
metabolism, and blood pressure are beginning to emerge (Barrett-Connor &
Bush, 1991).
Orally administered estrogen affects lipid metabolism in several ways
(Guetta & Cannon, 1996). Estrogen reduces LDL cholesterol by accelerating
the conversion of hepatic cholesterol to bile acids and increasing the
expression of LDL receptors upon cell surfaces. This leads to increased
clearance. HDL cholesterol is increased by an enhanced production of
apolipoprotein A-l and a decrease in hepatic lipase activity. These actions
are dependent upon the absorption of estrogen from the gut, rendering
transdermal estrogen replacement less effective than oral estrogen in terms
of serum lipid alterations (Guetta & Cannon).
A number of studies involving estrogen replacement and favorable
alterations in lipid profiles have been performed. Bush et al. (1987) followed
2270 postmenopausal women in the Lipid Research Clinics Prevalence
Study. After an 8.5 year follow-up estrogen users had significantly (p <
23
0.05) higher HDL-C and triglyceride levels and significantly lower LDL-C
levels than nonusers. Matthews et al. (1989) performed a 5 year study of 541
premenopausal women making a transition into menopause in order to
determine changes in CVD risk factors. It was found that after menopause,
women taking estrogen therapy had significantly (p < 0.05) higher levels of
triglycerides and apolipoprotein A-l than nonusers. Estrogen users also had
lower levels of LDL cholesterol and higher levels of HDL cholesterol than
nonusers, but these results were not found to be statistically significant
(Matthews et al.).
In addition to serum lipoproteins, estrogen has been identified as
having a relationship to other CVD risk factors. Nabulsi et al. (1993)
performed a cross sectional analysis of the data from the Atherosclerosis
Risk in Communities study. A sample of 4958 postmenopausal women were
divided into one of four groups: (a) current users of estrogen, (b) current
users of estrogen and progestin, (c) nonusers who formerly used hormones,
(d) nonusers who had never used hormones. The factors analyzed included
serum lipoprotein levels, hemostatic factors, carbohydrate metabolism, and
blood pressure. The study had two main hypotheses: that there would be
significant differences in risk factors between users of hormone therapy and
nonusers, and that there would be significant differences between those
24
using unopposed estrogen therapy and those using combination therapy. The
results showed that unopposed estrogen users had significantly (p< 0.001)
higher levels of triglycerides than both nonusers and users of combined
therapy. Users of unopposed estrogen and combination therapy had similar
levels of HDL cholestreol, both being significantly (p < 0.001) higher than
nonusers. LDL cholesterol levels were similar in both groups of estrogen
users, and were significantly (p < 0.05) lower than the levels of nonusers.
Mean fibrinogen levels were similar in both groups of estrogen users, and
were significantly (p < 0.001) lower than in nonusers. Similar levels of
serum glucose were also found in both estrogen replacement groups, with
significantly (p < 0.001) lower levels than nonusers. No significant
differences in systolic or diastolic blood pressure were observed between
any of the groups (Nabulsi et al.).
Primary Prevention. A number of studies regarding the use of both
unopposed estrogen and estrogen/progestin in the prevention of CVD risk
have been published. The Postmenopausal Estrogen/Progestin Interventions
(PEPI) Trial (Writing Group, 1995) studied unopposed estrogen and
estrogen/progestin regimens as primary prevention for CVD risk factors in
healthy women. PEPI was a 3 year, multicenter, randomized, double-blind,
placebo controlled trial of 875 postmenopausal women with no evidence of
25
cardiovascular disease. The women were divided into three treatment
groups: placebo, unopposed estrogen, and estrogen/progestin. The results
showed that the women in both active treatment groups had significantly
higher HDL cholesterol levels than the placebo group, with those on
unopposed estrogen having a significantly higher HDL cholesterol than
those receiving combination therapy. LDL cholesterol levels were
significantly lower in both active treatment groups than in the placebo
group. Triglycerides were significantly higher in both active treatment
groups in comparison to placebo treated women. No significant differences
in blood pressure or glucose and insulin were observed between any of the
groups. Placebo subjects had significantly higher levels of fibrinogen than
treatment groups, as well as a significantly higher weight gain than treatment
groups. The PEPI researchers concluded that unopposed estrogen was the
treatment of choice in order to increase HDL cholesterol in women without a
uterus, and estrogen with cyclic medroxyprogesterone was the treatment of
choice in women with an intact uterus (Writing Group, 1995).
Grodstein et al. (1996) also conducted a study in order to compare the
effectiveness of estrogen/progestin and unopposed estrogen regimens in the
prevention of CVD. These researchers followed the subjects (n = 59,337) of
the Nurses’ Health Study who were ages 30 to 55 at baseline, for a period of
26
16 years. They found that the risk of CVD in women who used
estrogen/progestin regimens was significantly lower than among nonusers,
and that this reduction was similar to the risk reduction conferred by
estrogen alone (Grodstein et al.).
Secondary Prevention. The Heart and Estrogen/Progestin
Replacement Study (HERS) looked at the effects of unopposed estrogen and
estrogen/progestin regimens as prevention for recurrent CVD events in
women with pre-existing CVD (Hulley et al., 1998). HERS was a
randomized, blinded, placebo controlled trial involving 2763 women with
coronary artery disease. The women were divided into two groups: one
group given placebo and another given CEE with progesterone. The women
were then monitored over a 4 year period for the development of nonfatal
myocardial infarction, death due to CVD, coronary revascularization
procedures, congestive heart failure, unstable angina, stroke, and peripheral
vascular disease. The researchers found no significant differences between
the two groups in any of the above outcomes, however, a significantly
higher incidence of venous thromboembolic events and gallbladder disease
was seen in the hormone group. From these data, it was recommended that
hormone therapy not be initiated as a means of secondary prevention for
recurrent CVD, however it would be appropriate for women receiving
27
therapy pnor to a CVD event to continue therapy after the event (Hulley et
al.).
The Women’s Health Initiative (WHI), recently initiated by the
National Institute of Health, is the largest United Sates prevention study of
its kind. It will involve three major components: (a) randomized controlled
clinical trials of approaches to prevention coronary disease, breast cancer,
and hip fractures in women, (b) observational studies to identify predictors
of disease, and (c) community study of approaches to identify healthy
behavior development (Rossouw et al., 1995). Approximately 63,000
women will be enrolled in clinical trials which will be performed at 40
centers across the United States. Ten of these centers focus on the
recruitment of minority populations. Hormone therapy will be represented in
one of the clinical trials, with the primary outcome of the trial being
coronary artery disease. Results of the WHI will be available by the year
2007 (Rossouw et al., 1995).
Summary
This chapter provided an ov<'erview of the role of estrogen in the
prevention of CVD. Examples of the differences in cardiovascular morbidity
and mortality between men and women were
provided. Physiologic
consequences of menopause were also discussed, as well as methods of
28
hormone therapy. A discussion of the results of various studies regarding the
effects of estrogen upon the development of CVD, and the role of estrogen
in primary prevention of CVD and in the prevention of recunent CVD
events was given. As indicated by this literature review, further research into
the relationship between estrogen therapy and CVD is needed.
29
Chapter 3
Methodology
The purpose of this study was to analyze the relationship between
postmenopausal estrogen replacement and coronary artery disease (CAD),
giving consideration to the other coexisting CAD risk factors of smoking,
hypertension, diabetes mellitus, obesity, and history of CAD. This chapter
provides a description of the methodology used to obtain and analyze data.
A discussion of the research hypothesis, research design, instrumentation,
sample, setting, and procedure are included in this chapter. Operational
definitions are provided in this chapter. Protection of human rights is
discussed. The pilot study and method of data analysis are also described.
Hypothesis
There was a statistically significant inverse relationship between
estrogen use in postmenopausal women and the presence of CAD.
Operational Definitions
The following terms are defined as they were used in this study.
1. Coronary artery disease is the angiographic presence of one or more
lesions with a 50% or greater obstruction of coronary vessel lumen m a
symptomatic individual. All angiography results were obtained and
interpreted by board certified cardiologists.
30
2. Diabetes mellitus was present when a subject was taking oral
antihyperglycemic agents, oral insulin sensitizing agents, or insulin via daily
injections or an insulin pump.
3. Estrogen therapy was the use of either unopposed estrogen at a dose
of 0.625mg or greater on a daily basis, or combined estrogen (0.625mg or
greater) and progesterone 2.5mg or greater on a daily or cyclic basis.
Transdermal preparations were not considered as part of the definition of
estrogen replacement therapy in this study.
4. A history of CAD was present in a subject who had undergone
previous revascularization procedures (percutaneous transluminal coronary
angioplasty [PTCA], coronary artery bypass grafting) or who had been
diagnosed with a myocardial infarction prior to the current admission for
cardiac catheterization.
5. Hypertension was present when a subject was taking
antihypertensive medications at the time of the study.
6. Obesity was defined as having a body mass index (BMI) greater
than 28 kilograms per meters squared (kg/m2). The BMI was obtained by
pressed in kilograms by the height expressed
dividing the subject’s weight ex]
in meters squared.
31
7. A postmenopausal woman was one who has been amennorheic for
12 months or longer. Women who had undergone surgical procedures
leading to permanent amennorhea, such as bilateral oophrectomy, were also
enrolled in this study if those procedures had been performed more than
twelve months prior to the study.
8. Smoking was defined as the daily use of cigarettes or any other
tobacco products, such as cigars or pipes.
Setting
The setting for this study was a cardiac catheterization laboratory,
located within a 487 bed acute care facility in northwestern Pennsylvania.
The laboratory consisted of three catheterization suites and an eight bed
holding/recovery area. The laboratory averages over a total of 1,500 cardiac
catheterizations per year.
Sample
The sample of 36 subjects was obtained over a 4 week period from
February 21 through March 21,2000, from the population of women
presenting to the cardiac catheterization laboratory for left heart
catheterization (LHC). Inclusion criteria were that the subjects must be 5.0
years of age or older and amennorheic for 12 months or longer. During the
designated time frame, 39 surveys were completed. Three surveys were
32
discarded because they did not meet the inclusion criteria, for a final sample
size of 36. Of the 36 useable surveys, 100% of the subjects were 50 years of
age or older and at least 12 months postmenopausal. Of the 36 subjects, 9
were current estrogen users (25%), and 27 were nonusers (75%). All of the 9
subjects currently using estrogen had been receiving therapy for 6 months or
longer. Of the 27 nonusers, 5 subjects (18.5%) had taken estrogen in the
past, while the remaining 22 subjects (81.5%) had never taken estrogen. All
of the 5 subjects who were past users of estrogen had discontinued therapy
greater than 3 years ago.
Pilot Study
A sample of 16 charts from women 50 years of age and older who
underwent LHC was selected for the pilot study. These charts were reviewed
and data regarding estrogen therapy, smoking habits, hypertension, BMI,
and presence of cardiovascular disease were recorded and placed on a
contingency table. Chi-square was chosen as the method of data analysis
because the data obtained were nominal. A Chi-square analysis with a
statistically significant level of p=<0.05 was then performed for each risk
factor and the development of CAD. Pilot study results were reported in
aggregate and according to presence of each risk factor. Expected values
were calculated from the actual values. Significant differences were found
33
between the risk factors of smoking, hypertension, and obesity in the
development of CAD. A Chi-square analysis was also performed to
determine differences between estrogen users and nonusers in terms of the
development of CAD. No significant difference in the development of CAD
was found between the estrogen users and nonusers. This finding was
contradictory to other findings in the literature regarding estrogen and CAD.
The small sample size was a consideration, as was the accuracy of the
information found in the charts.
It was decided that subject interviews regarding estrogen therapy and
the other risk factors being studied would serve to increase the accuracy of
the data. It was also decided that questions regarding the duration of
estrogen replacement therapy, history of CAD, and diabetes mellitus would
be added to the survey in order to provide further clarification of the role of
estrogen in CAD development. No changes were made to the survey items
that addressed smoking, hypertension, and obesity.
Research Design
This study utilized a retrospective descriptive research desrgn. The
independent variables studied were postmenopausal estrogen replacement,
smoking habits, hypertension, obesity, diabetes mellitus, and history of
34
CAD. The dependent variable was the presence of CAD
to obtain data were subject interview and patient chart review.
Instrumentation
A researcher-designed survey was used as the research tool (Appendix
A). The survey was formatted for the use with an automatic survey scanning
machine. Questions 1 and 2 were used as criteria for subject eligibility to
participate in the study, determining subject age (equal to or greater than 50)
and menopausal status (no menstrual cycle for 12 months or longer). A
“yes” response was required for both items in order to be included in the
study.
Questions 3, 4, 5, and 6 classified estrogen use. Question 3 asked
about current estrogen use. Question 4 asked about the duration of current
estrogen therapy. Questions 5 and 6 were directed to the 27 subjects with a
“no” response to question 3 in order to determine past use of estrogen and
the amount of time elapsed since the cessation of therapy.
The risk factor of obesity was indirectly addressed with questions 7
and 8, which asked for the subject’s height in inches and weigh
kilograms. These values were used to calculate a body mass index (BMI) for
each subject. A value of 28kg/m! or greater was considered by the researcher
to be obese. Height and weight were omitted on one survey from a subject
35
Who had never used estrogen. A BMI eould not be calculated for this
subject, reducing the number of “never”
estrogen users to 21 for this
question only. The other responses in this particular survey were included in
the other data analyses. Question 9 concerned smoking habits at the time of
hospital admission. Question 10 addressed hypertensive status; only subjects
receiving antihypertensive medications were classified as being
hypertensive. Question 11 concerned the presence of diabetes mellitus; only
subjects receiving antihyperglycemic agents, insulin sensitizing agents, or
insulin by daily injection or insulin pump were classified as being diabetic.
Question 12 sought a history of CAD. Question 13 addressed the presence of
significant coronary artery lesions found during the subject’s
catheterizations.
Inter-rater Reliability
This survey was administered by 4 registered nurses instructed on the
study’s purpose, design, method of data collection, and protection of patient
confidentiality. In order to determine inter-rater reliability, a case study of a
fictitious patient (Appendix B) was given to the nurses, who were then asked
to fill out the survey using data from the case study. Agreement on 12 of
answer key statements was required for the nurses to be considered rehab
36
to collect data. All of the 4 nurses responded correctly on greater than 12
items on the sample survey.
Procedure
Upon arrival to the lab, each female patient 50 years of age or older
scheduled for LHC was approached by the researcher or research assistants.
The potential subjects were informed of the study’s purpose and the
information that would be required from them. They were then asked if they
would be willing to participate in the study. All research assistants followed
a standardized outline for obtaining oral informed consent (Appendix C).
Agreement to participate in the study was considered informed consent.
After consent was obtained, the researcher or research assistants
obtained subject data using the researcher-designed survey. Survey data
were collected via subject interview and chart review. Data obtained through
subject interview included postmenopausal status, estrogen use, smoking
habits, the presence of hypertension, diabetes mellitus, and history of CAD.
Chart review was utilized to obtain data regarding the subject s age, height
and weight and cardiac angiography results.
After the interview, the subjects underwent left heart catheterizatrons,
which were performed and interpreted by board cerufied cardiologists.
When the catheterizations were completed, the subject’s record was agam
37
reviewed to obtain coronary angiography results. These results were then
entered on the survey; the completed surveys were placed in a secured area.
Protection of Human Rights
All subjects entered into the study were informed of the purpose of the
study and of the information that would be obtained from them. All subjects
were ensured anonymity. All subjects were given the opportunity to decline
to participate in the study. Verbal agreement to participate in the study was
considered informed consent. Neither names nor medical record numbers
were placed on the survey. The surveys will remain secured for a period of 3
years at which time they will be destroyed. Only grouped data were
reported. Permission to perform the study was obtained from the medical
director of the cardiac catheterization laboratory, and the department team
leader (Appendix D), and the institution’s review board (Appendix E).
Data analysis
The responses to the survey were analyzed using descriptive and
inferential statistics, and nonparametric testing. The AutoData® Survey
software was used to tabulate the responses to the survey. The Statistical
Package for the Social Sciences (SPSS®) Base
1988 was utilized for data analysis.
8.0 for Windows, copyright
38
The results of the study were reported in aggregate according to types
of estrogen users (current use, past use, never used), presence of each risk
factor, and presence of CAD on cardiac catheterization. The data presented
were nominal (categorical) and dichotomous, and were analyzed using
descriptive and inferential statistics and nonparametric techniques. All data
were placed into contingency tables of varying size for the determination of
independence between each type of estrogen user groups, and for the
measurement of relationships between presence of each risk factor, estrogen
use and CAD. Because some of the expected cell frequencies had values less
than 5, a Fisher’s exact test of probability was used to determine
independence between estrogen user groups, with expected responses being
derived from the actual numbers.
As the contingency tables were larger than 2 x 2, a Cramer s V (F)
was selected to measure relationships. All percentages were calculated to
two decimal points and rounded to one decimal point. If a value after the
decimal point was greater than or equal to .05, it was rounded to the next
highest number. A level of significance ofp=0.05 was established for all
calculations. Categories for the V value (indicating relationship strength)
were obtained from Munro and Page (1986) and classified as follows: (a)
39
0.00-0.25 little if any, (b) 0 26-9.49 low, (c) 0.50-0.69 moderate, (d) 0.70-
0.89 high, (e) 0.90-1.0 very high.
Subjects were initially classified into two groups of estrogen users,
current users and nonusers. After examination of the data from questions 3
through 6 of the survey, the original two groups were reclassified into three
groups. The group of current users stayed the same, however, nonusers were
divided into two separate groups: those who had used estrogen in the past
(greater than 3 years), and those who had never used estrogen. After the
subjects were classified into estrogen user groups, tests for independence
among the groups in terms of risk factors were performed using Fisher’s
exact test. The presence of each risk factor was calculated for each
classification of estrogen user.
The next step of data analysis was the evaluation of relationships
between estrogen use and presence of CAD, and risk factors and presence of
CAD within each group of estrogen users. After the Cramer s V for the
relationship between estrogen use and CAD was
obtained, the relationship
between presence of risk factors and presence of CAD for each group of
estrogen user was performed. A contmgency table was constructed for each
,fCAD and presence or absence of each of
according to presence or absence o
40
the five risk factors. Percentages for each value in the table were calculated
by dividing the number of subjects with (or without) each risk factor by the
total amount of subjects with (or without) CAD. This percentage reflected
the prevalence of each risk factor among subjects with or without CAD. In
addition to the analysis of relationship between each risk factor and CAD,
the data were also examined for trends in the prevalence of particular risk
factors in those with and without CAD.
Summary
The purpose of this study was to analyze the relationship between
postmenopausal estrogen therapy and CAD, giving consideration to the
other coexisting CAD risk factors of smoking, hypertension, diabetes
mellitus, obesity, and history of CAD. This chapter provided a description of
the methodology used to perform this analysis, including research design,
protection of human rights, hypothesis, instrumentation, setting, sample and
procedure. Operational definitions for this study were provided, and the
method of data analysis in the pilot study was discussed.
41
Chapter 4
Results
The purpose of this study was to analyze the relationship between
postmenopausal estrogen therapy and the presence of coronary artery disease
(CAD), giving consideration to five other possible coexisting CAD risk
factors of obesity, hypertension, cigarette smoking, diabetes mellitus, and
previous history of CAD. It was hypothesized that there was a statistically
significant inverse relationship between CAD and estrogen use in
postmenopausal women. The data for the study were obtained using a
researcher-designed survey (Appendix A) that entailed a subject interview
and review of the subject’s medical record. The results of this survey are
presented in this chapter.
Tests of Independence
The subjects were classified into groups of current users of estrogen
(n==9), past users of estrogen (n=5), and those who had never used estrogen
(n=22). A Fisher’s exact test was used to determine independence am g
groups of estrogen users in terms of presence of CAD and presence of the
risk factors of obesity, smoking, hypertension, diabetes melhtus, and history
of CAD.
42
Presence of CAD. The data regarding estrogen use and presence of
CAD are presented m Table 1. The lowest rate of CAD was observed in the
group of past estrogen users, with the highest rate being observed in the
group of current estrogen users. A Fisher’s exact test showed that when
compared to expected, there were no statistically significant differences
among the three groups of estrogen users and presence of CAD.
Table 1
Estrogen Use and Presence of CAD
Estrogen Use
CAD
Current
(n=9)
Total
(N=36)
n
(%)
n
(%)
Never
(n=22)
Past
(n=5)
n
(%)
n
(%)
Yes
26 (72.2%)
7 (77.8%) 2 (40.0%) 17(77.3%)
No
10 (27.8%)
2 (22.2%) 3 (60.0%)
5(22.7%)
Obesity. Of the 35 subjects with a response to this question, 23
(65.7%) were classified as obese. Hie lowest incidence of obesity (20%) was
43
noted in the group of past estrogen users. A Fisher’s exact test showed no
statistically significant differences among the three groups of estrogen users
in the presence of obesity. The data on obesity and estrogen use are
summarized in Table 2.
Table 2
Estrogen Use and Obesity
Estrogen Use
Obesity
Total
(N=35)
n
(%)
•
n
Never
(n=21)
Past
(n=5)
Current
(n=9)
(%)
n
(%)
n
(%)
Yes
23 (65.7%)
7 (77.8%)
No
12 (34.3%)
2 (22.2%) 4 (80.0%) 6(28.6%)
1 (20.0%) 15(71.4%)
Note, One survey was omitted from “never•” users due to incomplete
information for this item.
Smoking. Of the 36 subjects, 6 were smokers (16.7%), and 30 were
nonsmokers (83.3%) at the time of admission. Subjects who had used
estrogen in the past had the highest smoking rates (20%), with the lowest
rates (11.1%) being observed in the current estrogen users. The data for
44
smoking and estrogen use are presented in Table 3. A Fisher’s exact test
showed no statistically significant differences in smoking among the three
groups of estrogen users.
Table 3
Estrogen Use and Smoking
Estrogen Use
Smoking
Total
(N=36)
n
Yes
No
Current
(n=9)
(%)
6 (16.7%) •
30 (83.3%)
n
Never
(n=22)
Past
(n=5)
(%)
n
(%)
n
(%)
1 (11.1%)
1 (20.0%) 4(18.2%)
8 (88.9%)
4(80.0%) 18(81.8%)
Hypertension. Of the 36 subjects, 28 (77.8%) were classified as
hypertensive and 8 (22.2%) were classified as nonhypertensive. The rates of
hypertension were similar between the group who had never used estrogen
(81.8%) and the group of past users (80%). Current estrogen users had the
lowest incidence (66.7%) of hypertension (Table 4). A Fisher’s exact test
showed no statistically significant differences in presence of hypertension
among the three groups of estrogen users.
45
Table 4
Estrogen Use and Hypertension
Estrogen Use
Hypertension
Total
(N=36)
n
Current
01=9)
(%)
n
Never
(n=22)
Past
(n=5)
(%) n
(%)
n
(%)
Yes
28 (77.8%)
6 (66.7%) 4 (80.0%)
18(81.8%)
No
8 (22.2%)
3 (33.3%) 1 (20.0%)
4 (18.2%)
Diabetes. The risk factor of diabetes was classified according to each
group of estrogen users (Table 5). Of the 36 subjects, 7 (19.4%) were
classified as diabetics and 29 (80.6%) were classified as nondiabetics. The
highest incidence of diabetes (27.3%) was observed in the subjects who had
never taken estrogen. The lowest incidence (0%) was in the subjects with a
past use of estrogen. A Fisher’s exact test showed no statistically significant
differences in the incidence of diabetes among the three groups.
History of CAD. Of the 36 subjects, 14 (38.9%) had a history of
CAD, with the highest incidence of prior history in current estrogen users. A
46
Table 5
Estrogen Use and Diabetes
Estrogen Use
Diabetes
Total
(N=36)
n
Current
(n=9)
(%)
n
Past
Never
(n=22)
05)
(%)
n
(%) n
(%)
Yes
7 (19.4%)
1 (11.1%)
0
No
29 (80.6%)
8 (88.9%)
5 (100.0%) 16(72.7%)
(0.0%) 6 (27.3%)
Fisher’s exact test showed no statistically significant difference in CAD
history among the three groups (Table 6).
Relationship and Trend Analysis
After tests of independence were performed, relationships between
estrogen use and presence of CAD, and risk factors and presence of CAD for
each group of estrogen users were analyzed using Cramer s V.
The relationship between estrogen use and presence of CAD was the
first relationship to be summarized (Table 1).
47
Table 6
Estrogen Use and History of CAD
Estrogen Use
History of CAD
Total
(N=36)
n
Current
(n=9)
(%)
n
Past
(n=5)
(%) n
Never
(n=22)
(%)
n
(%)
Yes
14 (38.9%)
4 (44.4%) 2 (40.0%) 8 (36.4%)
No
22 (61.1%)
5 (55.6%) 3 (60.0%) 14 (63.6%)
A Cramer’s V showed a low positive correlation (Y=0,26) between the
variables of estrogen use and CAD, however, this value was not statistically
significant.
Current estrogen users. Two trends were noted within the group of
current estrogen users (n=9). The first was that 100% of the subjects without
CAD (n=2) were nonsmokers. The second was that both of the subjects
without CAD were nondiabetics. Cramer’s V showed little if any positive
relationships between each of the risk factors and presence of CAD. The risk
factor with the strongest relationship to presence of CAD was hypertension,
48
showing a low positive relationship, with a Vvalue of 0.38. The risk factor
with the weakest positive relationship to the presence of recurrent CAD was
history of CAD, with a V value of 0.06. None of the calculated V values
achieved a 0.05 level of significance. These data for the current estrogen
users are summarized in Table 7.
Past estrogen users. For the group of past estrogen users (n=5), two trends
emerged from the data. The first was that all subjects without CAD (n=3)
were nonsmokers. The second trend was that 100% of the subjects with
CAD (n=2) had a history of CAD and 100% of the subjects without CAD
(n=3) did not have a history of CAD. The V values for this group as
calculated by a Cramer’s V ranged from low to high. The Vvalue for the
relationship between diabetes and presence of CAD was not calculated for
this group due to an insufficient amount of data for calculation. The
strongest positive relationship was between the risk factor of history of CAD
and presence of CAD, with a V value of 1.00. This value was significant at
P=0.03. The weakest positive relationship was between obesity and CAD,
with a V value of 0.41. With the exception of CAD history, none of the
remaining rvalues were found to be significant at a level of 0.05. The data
for presence of risk factors and CAD are summarized in Table 8.
49
Table 7
Risk Factors and Presence of CAD in Current Users of Estrogen (N=9)
Presence of CAD
Total
(N=9)
Yes
(n=7)
Risk Factor
n
n
Obesity
Yes
7
5 (71.4%)
2
2 (28.6%)
1
1
No
8
HTN
Yes
No
No
Smoking
Yes
Diabetes
Yes
No
History
Yes
No
V
No
(n=2)
(%)
(%)
n
2 (100.0%)
0.29
0
(0.0%)
(14.3%)
0
(0.0%)
6
(85.7%)
2 (100.0%)
6
4
(57.1%)
2 (100.0%)
3
3
(42.9%)
0
(0.0%)
(14.3%)
0
(0.0%)
1
1
8
6
(85.7%)
4
3
(42.9%)
5
4
(57.1%)
0.19
0.38
0.19
2 (100.0%)
1
(50.0%)
1
(50.0%)
0.06
50
Table 8
Risk Factors and Presence of CAD in Past Users of Estrogen (N=5)
Presence of CAD
Total
(N=5)
Yes
(n=2)
V
No
(n=3)
n
Risk Factor
n
n
Obesity
Yes
1
0
4
2 (100.0%)
2 (66.7%)
1
1 (50.0%)
0
No
4
1 (50.0%)
3 (100.0%)
HTN
Yes
4
1 (50.0%)
3 (100.0%)
No
1
1 (50.0%)
0
(0.0%)
0
0
(0.0%)
0
(0.0%)
5
2 (100.0%)
3 (100.0%)
2
2 (100.0%)
0
3
0
No
Smoking
Yes
Diabetes
Yes
No
History
Yes
No
(%)
(0.0%)
(%)
1 (33.3%)
0.41
(0.0%)
*Note: Insufficient data to calculate V
(0.0%)
0.61
0.61
*
(0.0%)
1.0
3 (100.0%)
51
Never estrogen users. A trend appearing from the data in the group of those
who had never used estrogen (n=22) was that 100% of the subjects without
CAD (n—6) were nonsmokers. The relationships between each risk factor
and presence of CAD were then analyzed for the group of subjects who had
never used estrogen (n—22). The strength of the relationships between risk
factors and presence of CAD within the group of those who had never used
estrogen ranged from little to low. The relationship with the strongest
positive relationship within this group was between obesity and presence of
CAD, with a Vvalue of 0.38. The weakest positive relationship within this
group was between diabetes and presence of CAD, with a V value of 0.15.
None of the calculated K values were found to be significant at the 0.05
level. These data on risk factors and presence of CAD in subjects never
using estrogen can be found in Table 9.
Summary
This chapter has presented the results of a study of postmenopausal
women undergoing left heart catheterization. The subjects (N=36) were
placed into three groups according to estrogen use: current (n=9), past (n=5),
and never (n=22). The results of this study were analyzed using descriptive
and inferential statistics, and nonparametric testing. Fisher’s exact test was
52
Table 9
Bisk Factors and PresencetrfCADin Never Users of Bstrouen (N-m
Presence of CAD
Total
(N=22)
Yes
(n=16)
No
(n=6)
V
Risk Factor
n
n
(%)
n
(%)
Obesity*
Yes
15
12 (75.0%)
3
(60.0%)
No
Smoking
Yes
0.38
6
4 (25.0%)
2 (40.0%)
4
4 (25.0%)
0
(0.0%)
0.29
No
18
12 (75.0%)
6 (100.0%)
HTN
Yes
18
14 (87.5%)
4
(66.7%)
0.24
No
Diabetes**
Yes
No
History**
Yes
No
4
2 (12.5%)
2
(33.3%)
6
5(31.3%)
1
(16.7%)
16
11 (68.8%)
8
7 (43.8%)
1
14
9 (56.3%)
5 (83.3%)
‘Note: Data on one survey insufficient to calculate BMI.
**Note: Percentages >100 due to method o roun g
0.15
5 (83.3%)
(16.7%)
0.25
53
used to determine the mdependence between the three groups of estrogen
users in terms of the presence of CAD and presence of obesity, smoking,
hypertension, diabetes, and CAD history. No statistically significant
differences were found among the three groups of estrogen users in terms of
the presence of CAD. There were no statistically significant differences
between the three groups of estrogen users in the presence of the five risk
factors considered in this study.
After tests for independence were performed, the relationship
between estrogen use and the presence of CAD was analyzed. The
relationships between the presence of each risk factor and the presence of
CAD were analyzed according to each group of estrogen users. A Cramer’s
V was used for relationship analyses. A low positive (PM).26) correlation
between estrogen use and CAD was found, however, this value was not
significant at ^=0.05. The relationship between history of CAD and presence
of CAD in past users of estrogen was positive (7-1.0) and significant at the
0.03 level. The strength of the relationships between risk factors and the
presence of CAD in the remaining groups ranged from little, if any to
moderate, however, none of these values were significant at/? 0.05.
54
Chapter 5
Discussion
This chapter provides a discussion of this study of estrogen use and
presence of coronary artery disease (CAD) in postmenopausal women. The
findings of the study are summarized and then compared to other studies in
the literature. The findings are then related to the theoretical framework used
for this study and relevance of the findings to the nurse practitioner is
discussed. Conclusions and recommendations for further research are also
provided in this chapter.
A researcher-designed survey was administered to postmenopausal
women undergoing left heart catheterization in a cardiac catheterization
laboratory located in an acute care facility in northwestern Pennsylvania.
The subjects were categorized into three groups: current estrogen users, past
estrogen users, and those who had never used estrogen. An analysis of the
risk factors of obesity, smoking, hypertension, diabetes mellitus, and history
of CAD was performed for each group. Data were analyzed using
descriptive statistics and nonparametric tests.
In this study, it was hypothesized that there was an mverse
relationship between estrogen use and the presence of CAD in
postmenopausal women. The hypothesis was rejected. Analy
55
relationship with Cramer’s V demonstrated a low positive correlation
(V=0.26) between estrogen use and presence of CAD, however, this value
was not significant at the 0.05 level. A similarity can be drawn between this
result and the results of the Heart and Estrogen/Progestin Replacement
Study (HERS). In studying estrogen use in postmenopausal subjects with
established CAD, HERS researchers found no significant reduction in
recurrent coronary events in subjects taking estrogen (Hulley et al., 1998).
Although this study did not limit subjects to those with established CAD, the
rates of history of CAD were highest in the group of current estrogen users.
In this study, the overall prevalence of CAD in the entire sample
(N=36) was 72.2%. It was anticipated at the onset of the study that CAD
would be more prevalent in this sample as it was derived from the
population referred to a cardiac catheterization laboratory. The differences in
the presence of CAD among the estrogen using groups were not found to be
statistically significant using a Fisher’s exact test. The lowest incidence of
CAD was in past users of estrogen, all of whom had discontinued estrogen
therapy 3 years ago or longer. The low incidence of CAD in past users m
this study was in contrast to the findings from the Nurses’ Health Study
(Grodstein et al., 1996). In the Nurses’ Health Study, the protective benefit
of estrogen against CAD began to diminish 3 or more years after therapy
56
was stopped. The favorable risk profile observed in this study for past users
of estrogen, who had the lowest rates of obesity, diabetes mellitus, and CAD
history, may provide an explanation for this observation.
Risk factor analysis for the presence of obesity, smoking,
hypertension, diabetes mellitus, and CAD history showed no statistically
significant differences between the three groups of estrogen users. One
pattern of risk factors noted in this study was that current estrogen users had
the lowest rates of smoking and hypertension. Although the past users had
the lowest incidence of diabetes, current users had a lower incidence of
diabetes than those who had never used estrogen. These results can be
compared to a study performed by Matthews et al. (1996) to determine if
estrogen users had a better cardiovascular risk profile than nonusers.
Matthews et al. found that prior to initiating therapy, estrogen users had
lower blood pressure, lower weight, and lower fasting insulin levels than
nonusers. In contrast, estrogen users had the highest rates of obesity in this
study. However, another study performed by Matthews et al. (1989) found
no statistically significant difference in postmenopausal weight gain between
estrogen users and nonusers, nor did estrogen users lose weight after
initiating therapy. Researchers of the Postmenopausal Estrogen/Progestm
57
Interventions (PEPI) trial (Writing group, 1995) also noted that waist-hip
ratio increased over time at a similar rate in users and nonusers of estrogen.
The lower rate of hypertension in the current estrogen users of this
study is unlikely to be related to estrogen use. It was noted in the PEPI trial
that there were no significant differences in systolic or diastolic blood
pressure between estrogen users and nonusers (Writing group, 1995). It is
possible, as noted in Matthews et al. (1996), that estrogen users are more
compliant individuals who are more likely to follow diet and exercise
regimens, both of which would favorable impact blood pressure.
This study also analyzed the relationships between each of the five
risk factors and presence of CAD within each of the estrogen groups. No
statistically significant relationships were found, with the exception of CAD
history and presence of CAD in the past users. A trend that emerged from
the data was that 100% of the subjects without CAD in all groups of
estrogen users were nonsmokers.
Conclusions
Several factors contributing to the rejection of the hypothesis were
identified. One factor that influenced this was the small sample size, which
led to a less than desired number of estrogen users available for analysis.
The small sample size also impacted the calculations. A second factor was
58
that the sample was taken from a population with a higher prevalence of
CAD than the general population. Another possible contributing factor was
that the estrogen users in this study had higher rates of obesity and CAD
history than the past users and never users. It was also noted that the
influence of other CAD risk factors, such as hyperlipidemia, homocystine,
and positive family history, were not included in this study. The combination
of these other risk factors with the risk factors considered in the study may
have had an unidentified impact upon the presence of CAD in the subjects.
Although the results of this study cannot be generalized to the overall
population of postmenopausal women, this study does provide information
that is relevant to the nurse practitioner managing the health of
postmenopausal women. Similar to the results of HERS, this study does not
provide evidence supporting the initiation of estrogen therapy in
postmenopausal women who have a history of a CAD event. The benefit of
initiation of estrogen therapy prior to a CAD event cannot be inferred from
this study. However, the benefits of risk factor modification such as weight
loss and smoking cessation for the promotion of cardiovascular health can be
inferred from the results of this study.
The findings of this study can be related to the nurse practitioner
functioning within Orem’s Self-care Deficit Theory. Based on Orem’s
59
theory, menopause was identified as an existing condition that has a possible
deviation of the development of CAD. Estrogen therapy was identified as a
possible health care deviation requisite of the postmenopausal woman
Although the findings of this study were unable to support the hypothesis of
estrogen therapy as a health deviation requisite, other requisites for the
prevention of CAD were identified. These would include weight control,
smoking cessation, and adequate control of hypertension and diabetes
mellitus. Nursing agency, as related to this study would involve the nurse
practitioner’s ability to identify and appropriately manage the requisites of
risk factor modification.
Recommendations for Future Research
Recommendations for future research were derived from the initial
limitations of this study and from the results of this study.
1. Replicate this study with a larger sample size to include estrogen
users of greater than and less than 6 months duration, and past users who
discontinued therapy in less than 3 years ago.
2. Replicate this study at different facilities and at different locations.
3. Replicate the study and include other risk factors such as
hyperlipidemia, homocystinemia, and positive family history.
60
4. Perform a similar study with the addition of calculating the weight
of each risk factor in the development of CAD in both users and nonusers of
estrogen.
5. Perform a follow-up study of estrogen nonusers with and without
CAD on catheterization for future recurrent CAD events following the
initiation of estrogen therapy prior to hospital discharge.
Summary
This chapter provided a discussion of study results. The hypothesis of
the study was rejected and circumstances influencing this finding were
identified. It cannot be inferred from the results of this study that estrogen
use leads to a decrease in CAD. The results of this study were compared to
results of larger studies published in the literature regarding estrogen use and
CAD. Providing instruction and assisting with risk factor reduction was
identified as a task of the nurse practitioner functioning within a supportive-
educative nursing system as part of Orem’s Theory of Self-care.
The conclusions of this study were discussed and recommendations for
future research were mentioned.
61
References
American Heart Association (1999). Heart and stroke facts: 1999
statistical supplement, Granville, TX: Author.
Barrett-Connor, E., & Bush, T.L. (1991). Estrogen and coronary heart
disease in women. JAMA ,265.1861-1867.
Bush, T.L., Barrett-Connor, E., Cowan, L.D., Criqui, M.H., Wallace,
R.B., Suchindran, C.M., Tyroler, H.A., & Rifkind, B.M. (1987).
Cardiovascular mortality and noncontraceptive use of estrogen in women:
Results from the lipid research clinics program follow-up study. Circulation,
75,1102-1109.
Barry, W.H. (1996). Cardiac catheterization and angiography. In J.C.
Bennett & F. Plum (Eds.), Cecil textbook of medicine (24th ed.) (pp. 208211). Philadelphia: W.B. Saunders Company.
Friedewald, W.T. (1996). Epidemiology of cardiovascular diseases. In
J.C. Bennett., & F. Plum (Eds.), Cecil textbook of medicine (24th ed.) (pp.
170-173). Philadelphia: W.B. Saunders Company.
Greendale, G.A., & Judd, H.L. (1995). Hormone therapy in the
menopause. In P.L. Carr, K.M. Freund, & S. Somani, (Eds.), The medical
care of women (pp. 635-642). Philadelphia: W.B. Saunders Company.
62
Grodstein, F., Stampfer, M.J., Manson, J.E., Colditz, G.A., Willett,
W.C., Rosner, B., Speizer, F.E., & Hennekens, C.H. (1996). Postmenopausal
estrogen and progestin use and the risk of cardiovascular disease. The New
England Journal of Medicine, 335. 453-461.
Guetta, V., & Cannon, R.O. (1996). Cardiovascular effects of estrogen
and lipid lowering therapies in postmenopausal women. Circulation^ 93
1928-1937.
Hartweg, D.L. (1991). Dorthea Orem: Self-care deficit theory. In C.
Metzger McQuiston & A.A. Webb. (Series Eds.), Notes on nursing theories:
Vol 4. (pp. 1-59).
Hulley, S., Grady, D., Bush, T., Furberg, C., Herrington, D., Riggs,
B., & Vittinghoff, E. (1998). Randomized trial of estrogen plus progestin for
secondary prevention of coronary heart disease in postmenopausal women.
JAMA, 280, 605-613.
Matthews, K.A., Kuller, L.H., Wing, R.R., Meilahn, E.N., & Platinga,
P. (1995). Prior to use of estrogen replacement therapy, are users healthier
than nonusers? American Journal of Epidemiology, 143, 971-978.
Matthews, K.A., Meilhan, E., Kuller, L.H., Kelsey, S.F., Caggiula,
A.W., & Wing, R.R. (1989). Menopause and risk factors for coronary heart
disease. The New England Journal of Medicine, 321,641-646.
63
Mosca. L. Manson. IE.. Sutherland, S.E., Langer, R.D., Manolio, T,
& Barrett-Connor, E. (1997). Cardiovascular disease in women: A statement
for healthcare professionals from the American Heart Association.
Circulation, 96, 2468-2482.
Munro, B.H. & Page, E.B. (1993). Statistical methods for health care
research. Philadelphia: J.B. Lippincott Company.
Murabito, J. (1995). Cholesterol screening and management. In P.L.
Carr, K. M. Freund, & S. Somam (Eds.), The medical care of women (pp.
531-541). Philadelphia: W.B. Saunders Company.
Orem, D.E. (1995). Nursing: concepts of practice (5th ed.). St. Louis:
Mosby-Year Book, Inc.
Nabulsi, M.B., Folsom, A.R., White, A., Patsch, W„ Heiss, G., Wu,
K.K., & Szklo, M. (1993). Association of hormone-replacement therapy
with various cardiovascular risk factors in postmenopausal women. The
New England Journal of Medicine, 328,1069-1075.
Ross, R. (1996). Atherosclerosis. In J.C. Bennett & F. Plum (Eds.),
Cecil textbook of medicine (24th ed.) (pp. 291-295). Philadelphia: W.B.
Saunders Company.
Rossouw, J.E., Finnegan. L.P., Harlan, W.R., Pmn, V.W., Clifford, C„
McGowan, J.A. (1995). The evolution of the Women s Health Initiativ
64
perspectives from the NIFL Journal of the Americaan Medical Women’s
Association 50(2), 50-55.
Sacks, F.M. (1995). Is there anything to add to our lipid risk factors
for coronary heart disease? The American Journal of Cardiology, 75,1263-
1264.
Wenger, N.K. (1995). Coronary artery disease. In P.L. Carr, K.M.
Freund, & S. Somani (Eds.), The medical care of women (pp. 543-552).
Philadelphia: W.B. Saunders Company.
Wenger, N.K., Speroff, L., & Packard, B. (1993). Cardiovascular
health and disease in women. The New England Journal of Medicine, 329,
247-253.
Wilson, P.W., Garrison, R.J., Castelli, W.P. (1985). Postmenopausal
estrogen use, cigarette smoking, and cardiovascular morbidity in women
over 50: The Framingham Study. The New England Journal of Medicine,
313,1038-1043.
Witzum, J.L, & Steinberg, D. (1996). The hyperlipoproteinemias. In
J.C. Bennett, & F. Plum (Eds.),
Cecil textbook of medicing (24th ed.) (pp.
1086-1095). Philadelphia: W.B. Saunders Company.
65
Writing group for the PEPI trial (1995). Effects of estrogen or
estrogen/progestin regimens on heart disease risk factors in postmenopausal
women. JAMA, 273,199-208.
66
Appendices
67
Appendix A
CAD and the Role of Estrogen Survey
B
Y
N
1. Is patient 50 years or older?
O O
2. Has the patient had a menstrual cycle within the last 12 months?
o o
3. Is the patient taking estrogen therapy (estrogen [premarin] or progestin/estrogen combinations
[prempro, premphase], do not include transdermal estrogen patches)?
o o
4. If yes to question 3, what is the duration of therapy?
O less than 6 months
O 6 months or greater
5. If no to question 3, has the patient taken estrogen therapy at any time since the onset of menopause?
Y
N
Y
N
O O
6. If yes to question 5, when was therapy stopped?
O less than 3 years ago
O 3 years or greater
7. Height in inches
8. Weight in kg
10. Is the patient receiving any antihypertensive medications?
o o
o o
11. Is the patient receiving any oral antihyperglycemic agents, insulin sensitizing agents, or insulin via injectio
or pump? ....................................................................................................................................................
o o
9. Is the patient a smoker at the time of this admission?
12. Does the patient have a history of CAD (history of cardiac cath showing lesions - or >50%,
previous MI, PTCA/Stent, CABG)?
...........................................................................
13. Presence of CAD on cath (lesion = or >50%)?
..............
Page 1
o o
o o
68
Appendix B
Case Study
The following case study was developed to demonstrate your
understanding of the survey that you will be administering to the subjects of
the study. Please read the case study carefully, then based on the information
of the case study complete the attached survey as if you were interviewing
an actual subject. Answer the questions only upon information presented in
the study.
P.R. is a 58 year old female patient scheduled for a left heart
catheterization. Upon her arrival, you inform her of the study’s purpose and
ask for her verbal consent to participate in the study. Upon interviewing her,
you find that she has not had a menstrual cycle in 4 years. She states that she
was taking premphase 1 year ago, but stopped therapy because of breast
tenderness. She is currently using an estraderm patch once a week to manage
signs and symptoms of menopause. She denies any smoking habit. She
states that she takes hydrochlorothiazide for her blood pressure and rezulin
400mg in the morning for her “sugar”. She also states that she had a cardiac
cath about 3 years ago, and she “didn’t think it showed anything”. After
speaking with the patient, you then look at the chart, which gives a height
and weight of 64” and 1551bs, respectively, and a history which reveals that
the patient had a cath 3 years ago, showing diffuse disease with blockages of
30-40%. P.R. is then taken for her procedure. Review of the chart after the
procedure shows that she now has a 90% lesion in her left circumflex artery.
69
Appendix C
Steps to Obtain Informed Consent
Thank you for participating in the process of data collection for this
study. The study that you are participating in is being performed as part of
the thesis requirement for the MSN degree at Edinboro University. In order
to ensure that the subjects are receiving information regarding participation
in the study in a consistent manner, please follow the guidelines provided
below when obtaining informed consent.
1. Determine initial eligibility for study participation (female patient over
age 50 scheduled for LHC).
2. Inform patient of the following information regarding the study:
• She is being asked to participate in a study of coronary heart disease
in postmenopausal women.
• Participation in the study is voluntary and will not affect outcome of
care received in the lab or amount of time spent in lab.
• All results of the study will be reported in a grouped format.
• All participants will remain completely anonymous.
• Participants will be asked questions regarding menopausal status, use
of estrogen therapy, and cardiovascular risk factors.
• The charts of the participants will be reviewed by the researcher or
assistant for information regarding height, weight, medications, and
results of cath.
• Participation in the study does not involve receiving any
experimental treatment or procedure, and the cardiac catheterization
procedure will be the same as nonparticipants.
3. Allow patient to ask questions regarding this information prior to
obtaining consent. If you are unsure of the answer, please locate the
researcher to assist you.
70
Appendix D
Application to Conduct Research
Page 3 of 3
Investigator’s Statement
I certify that all the information contained in this application is a true and accurate synopsis of the
planned research. I agree to abide by the decisions of the IRB, policies of Saint Vincent and regulations
of the FDA, DHHS and other appropriate agencies. I further a^rec to:
• notify the IRB of any adverse effects, either locally or nationally;
• make no changes except to eliminate immediate hazards and notify the IRB of those
changes;
• monitor the research and report as required;
• alert a subject that may be placed at risk or jeopardy; and
• notify the IRB at the conclusion of the study and submit aAvritten report on noteworthy
.
information or data.
-IODate
Principal Investigator’s Signature
Feasibility and Resources
I agree that it is feasible to conduct this research study in the designated area(s)
re
and can be conducted using Saint Vincent
Surgical
:p;
tel Oftcilities
tent Chair’s Signature
Date
Research Office
This research was deemed (at the time of application) to be in concert with Saint Vincent Health System
mission.
Research Coordinator*s Signature
Type of Research
Research study was:
3/12/99
Exempt
Expedited
Full Review
approved as presented (see letter in file)
delayed, changes required (see letter in file)
changes received on:
approval date:
:___
0 denied (see letter in file)
71
Appendix E
Saint Vincent Health
232 West 25 Street
Erie, Pennsylvania 16544
814/452-5000
Center
SAINT
VINCENT
February 16, 2000
Kris Komosa
Saint Vincent Health Center
232 West 25 Street
Cardiac Cath Laboratory
Erie, PA 16544
Dear Kris:
On February 16,1 approved through expedited review the opening of your protocol titled
“Estrogen Replacement Therapy and Coronary Artery Disease in Women.”
Be advised that as the approved clinical investigator, you will be required to present an
updated report in 5 months at the ERB meeting scheduled for July 17, 2000. Any proposed
changes in the research protocol affecting the subject must be brought to the attention of the
ERB prior to initiation. You, as the clinical investigator, are required to notify the ERB of all
local adverse events.
You may begin the study upon receipt of this letter. Please keep a copy of this letter with the
file about the study. Should you require additional support for your study, please call the
Research Office at (814) 452-5701.
Sincerely,
SAINT VINCENT HEALTH CENTER
Dorothy S. Carlson, DEd, RN, CIM
Secretary
Institutional Review Board
c: K. Komosa, RN
and cardiovascular disease in
women / by Kristine A. Komosa.
Thesis Nurs. 2900 K81p c.2
POSTMENOPAUSAL ESTROGEN THERAPY AND
CARDIOVASCULAR DISEASE IN WOMEN
By
Kristine A. Komosa RN, BSN
Submitted in Partial Fulfillment of the Requirements for
the Master of Science in Nursing Degree
Edinboro University of Pennsylvania
Approved by:
Jpuith Schilling, CRNP, PhD
Committee Chairperson
Date
2
Vd
Jo [?h Or. Cacchione, MD, FACC
mittee Member
Date
Dorothy \Stano Carlson, RN, DEd
Committee Member
Date
< ,^3
Abstract
Postmenopausal Estrogen Replacement Therapy and Cardiovascular Disease
in Women
The purpose of this study was to analyze the relationship between
postmenopausal estrogen therapy and the presence of coronary artery disease
(CAD), giving consideration to the other coexisting CAD risk factors of
obesity, smoking, hypertension, diabetes mellitus, and CAD history. A
retrospective descriptive research design was utilized. Data were collected
using a researcher-designed survey that included subject interview and
medical record review. The sample of 36 postmenopausal women was
classified into 3 groups according to estrogen use: current users (n=9), past
users (n=5), and those who had never used estrogen (n=22). The data were
analyzed using descriptive and inferential statistics and nonparametric tests.
A p=0.05 level of significance was used. A Fisher’s exact test showed no
statistically significant differences among the estrogen groups in the
presence of CAD or presence of obesity, smoking, hypertension, diabetes
mellitus, and CAD history. A Cramer’s V was used for analysis of
relationships in the study. A low positive correlation (PH).26) was found
between estrogen use and the presence of CAD, however this was not
statistically significant. A strong positive relationship (r=1.00) was found
'i
between history of CAD and presence of CAD in past users of estrogen
(n=5), which was significant at p=0.03. The benefit of estrogen therapy as a
means of CAD prevention in postmenopausal women cannot be inferred
from the results of this study.
Acknowledgements
I would like to take this opportunity to recognize the efforts of the
individuals who contributed to the development of this thesis. First, I would
like to acknowledge the committee members: Dr. Judith Schilling, for her
time as committee chair, Dr. Joseph Cacchione, for his clinical expertise,
and Dr. Dorothy Carlson, for her assistance and expertise with data analysis,
I have learned much from all of them. I would also like to recognize the
efforts of my coworkers, particularly Mike Ochalek, Cara Milani, Dana
Webb, and Linda Scanlon, their assistance with data collection was greatly
appreciated. Finally, I would like to thank my husband and family for their
patience and support throughout these months.
Ur
Table of Contents
Page
Abstract
ii
Acknowledgements
iv
List of Tables
ix
Chapter 1: Introduction
1
Background of the Problem
1
Statement of the Problem
3
Theoretical Framework
3
Self-Care
4
Self-Care Agency
5
Therapeutic Self-Care Demand
6
Self-Care Deficit
6
Nursing Agency
7
Nursing System
8
Statement of Purpose
8
Assumptions
9
Limitations
9
Definition of Terms
10
Summary.
12
Chapter 2 : Review of Literature
Cardiovascular Disease in Women
14
14
Mortality
14
Morbidity
15
Risk Factors
16
Menopause
17
Physiologic Consequences
18
Methods of Hormone Therapy
18
Role of Estrogen in the Prevention of CAD
20
Mechanisms of Action
22
Primary Prevention
24
Secondary Prevention
26
Summary
27
Chapter 3: Methodology
29
Hypothesis
29
Operational Definitions
29
Setting
31
Sample
31
Pilot Study
32
Research Design
33
Instrumentation..
34
Inter-rater Reliability
35
Procedure..
36
Protection of Human Rights
37
Data Analysis
37
Summary
40
Chapter 4: Results
41
Tests of Independence
41
Presence of CAD
42
Obesity
42
Smoking
43
Hypertension
44
Diabetes
45
History of CAD
45
Relationship and Trend Analysis
46
Current Estrogen Users
47
Past Estrogen Users
48
Never Estrogen Users
51
Summary
Chapter 5: Discussion....
writ
Conclusions
57
Recommendations for Future Research
59
Summary
60
References
61
Appendices
66
A. CAD and the Role of Estrogen Survey
67
B. Case Study
68
C. Steps to Obtain Informed Consent
69
D. Signed Application to Conduct Research
70
E. Institutional Review Board Letter
71
List of Tables
Table
Page
1. Estrogen Use and Presence of CAD
42
2. Estrogen Use and Obesity
43
3. Estrogen Use and Smoking
44
4. Estrogen Use and Hypertension
45
5. Estrogen Use and Diabetes
46
6. Estrogen Use and History of CAD
47
7. Risk Factors and Presence of CAD in Current Users of Estrogen
49
8. Risk Factors and Presence of CAD in Past Users of Estrogen
50
9. Risk Factors and Presence of Cad in Never Users of Estrogen
52
1
Chapter 1
Introduction
This chapter provides an overview of the problem of coronary artery
disease (CAD) in women and the role of estrogen therapy in its prevention.
Dorthea Orem’s (1995) Theory of Self-Care was used as the theoretical
framework for this study. The background of the problem and the statement
of the problem are addressed within this chapter. This chapter also considers
assumptions and limitations of the study, and provides a definition of terms;
Background of the Problem
Cardiovascular disease (CVD) is the leading killer of women, claiming
more than 500,000 American lives per year (American Heart Association
[AHA], 1999). CVD accounts for one in every two women’s deaths, in
comparison to the one in 27 deaths from breast cancer (AHA, 1999). Women
generally develop CVD 10 years later than their male counterparts, with an
average age of 72.5 years at diagnosis, in comparison to the age of 62.8 years
in men (AHA). The cardioprotective effects of estrogen are thought to play a
role in this age difference.
In 1992, the National Heart, Lung and Blood Institute held an
invitational conference entitled “Cardiovascular Health and Disease in
Women” (Wenger, Speroff, & Packard, 1993). The purpose of this conference
2
was to identify gaps in current knowledge about CVD in women in order to
improve the outcome of care. Some of the largest gaps in cardiovascular care
of women included evaluation and treatment, as well as prognosis (Wenger et
al.). Differences between men and women in the of treatment of CVD and
outcomes were identified:
1. Although women experience greater functional limitations due to
chest pain than men, they undergo intensive and invasive evaluation (such as
cardiac angiography) less frequently than men.
2. Women are less likely to be eligible for thrombolytic therapy
following myocardial infarction than men due to a later hospital presentation,
advanced age, and greater comorbid conditions.
3. Women who undergo coronary artery bypass grafting are usually
sicker at the time of surgery, are at a more advanced stage of illness, and
require surgery on a greater emergent basis than men.
4. Women have an overall worse prognosis than men following
myocardial infarction, even with the use of thrombolytics.
5. Women are also likely to have worse outcomes following
percutaneous transluminal coronary angioplasty (PTCA) or coronary artery
bypass grafting.
3
Estrogen has been shown to have a protective effect in the prevention
of cardiovascular disease in women, reducing risk by approximately 50%
(Nabulsi et al., 1993). Mechanisms include: (a) alteration of serum lipid
levels, with increased high density lipoprotein cholesterol (HDL-C) and
decreased low density lipoprotein cholesterol (LDL-C) in estrogen users, (b)
alteration of hemostatic factors such as fibrinogen, with decreased fibrinogen
levels in estrogen users, and (c) alterations of serum glucose and insulin, with
decreased fasting glucose and insulin in estrogen users (Nabulsi et al.).
Statement of the Problem
Cardiovascular disease is the number one cause of death in women,
carrying a higher mortality rate in women than men (AHA, 1999). Despite
this fact, women undergo less invasive and intense evaluation for this disease,
with poorer outcomes of treatment than men (Wenger et al., 1993). The use of
postmenopausal estrogen has been shown to reduce the risk of cardiovascular
disease in women (Nabulsi et al., 1993). Further research into the relationship
between estrogen and the development of cardiovascular disease has been
recommended (Wenger et al.).
Theoretical Framework
The theoretical framework used for this study was Dorthea Orem’s
Self-care Deficit Theory (Orem, 1995). Orem’s theory includes six core
4
concepts, linked by three interrelated theories. These concepts are related to
this research study and have implications for both the postmenopausal woman
or the nurse practitioner.
Orem s Self-Care Theory is comprised of three interrelated theories: (a)
theory of self-care, (b) theory of self-care deficit, (c) theory of nursing system
(Hartweg, 1991). These six core concepts are self-care, self-care agency,
therapeutic self-care demand, self-care deficit, nursing agency, and nursing
system. Orem (1995) also includes the peripheral concept of basic
conditioning factors, which influence certain patient and nursing ideas.
Self-Care. Self-care is defined by Orem (1995) as “the practice of
activities that individuals initiate and perform on their own behalf in
maintaining life, health, and well-being” (p. 117). For an individual to
perform a self-care action, he or she must have knowledge of this action and
its relation to health and well-being (Hartweg, 1991). The self-care action
must then be deliberately performed with a particular health goal in mind.
In relation to this study, the health goal is the prevention of coronary
artery disease in postmenopausal women. The risk of coronary artery disease
can be decreased with estrogen therapy (Grodstein et al., 1996). The self-care
action of the postmenopausal woman would be to acquire the information
needed to make a decision regarding estrogen therapy. In order to do this, she
5
must understand the increased risk of cardiovascular disease following
menopause in order to make a deliberate decision regarding the use of
estrogen therapy.
Self-care Agency. The second concept in Orem’s theory is the concept
of self-care agency, which is defined as the ability of an individual to engage
in self-care activity. These abilities are arranged in a hierarchical structure
with basic functional ability at the base, followed by power components such
as motivation and reasoning, and with the ability to determine the appropriate
actions and integrate them into daily routine at the top of the structure
(Hartweg, 1991). Basic conditioning factors that relate to this concept include
the individual’s age, gender, developmental stage, cultural background,
family, pattern of living, and environment (Hartweg).
In following Orem’s model, the postmenopausal woman would obtain
information regarding her risk of cardiovascular disease and make an
informed decision regarding the use of estrogen therapy. A conditioning
factor influencing her decision may be that a family member taking estrogen
developed breast cancer. She may strongly believe that this may happen to
her. Another conditioning factor may be her educational level. If she has a
below average reading level, she may not be able to comprehend available
6
literature. If she decided to begin estrogen therapy, she would then integrate
this into her daily lifestyle.
Therapeutic Self-care Demand. The third concept in Orem’s theory is
therapeutic self-care demand, which can be defined as all the self-care actions
that should be performed by an individual over time to maintain health. These
actions are also referred to as self-care requisites, which are divided into
universal requisites, developmental requisites, and health deviation self-care
requisites (Orem, 1995).
This study will address postmenopausal estrogen therapy as a health
deviation self-care requisite. Orem (1995) wrote that a health deviation self-
care requisite is something that either prevents further deviations due to a
present condition, or controls an existing deviation. In this study, menopause
is the existing condition that has a further deviation of coronary artery disease
in the absence of estrogen therapy. This study concerned the role of estrogen
as a health care deviation requisite of the postmenopausal woman.
Self-care-Deficit. The fourth concept of Orem s theory is self-care
deficit, which is the relationship between self-care agency and therapeutic
self-care demand (Orem, 1995). This relationship may show self-care agency
as greater than therapeutic self-care demand (TSCD), less than TSCD, or
equal to TSCD. Orem stresses that self-care deficit is not a disorder but an
7
expression of the relationship between these two concepts. A self-care deficit
must exist for the role of nursing to be legitimate (Hartweg, 1991).
In applymg the concept of self-care deficit to this study, a deficit would
occur in a postmenopausal woman who is not taking estrogen therapy and is
unaware of the cardiovascular risks. This would demonstrate a legitimate
need for the services of a nurse practitioner who would educate the woman
concerning the risks and benefits of estrogen therapy, prescribe the
appropriate therapy, and educate the woman on how to integrate this therapy
into her daily routine.
Nursing Agency. The fifth concept in Orem’s theory is nursing agency,
which is defined as the ability of the nurse to identify an individual’s self-care
requisites and to assist this individual in meeting these requisites (Orem,
1995). This ability has a base in the sciences, humanities, and nursing
experience over time, and vanes with individual nurses according to their
respective experiences and practice areas. Basic conditioning factors are also
applicable to this concept, in that the nurse’s age, developmental level,
cultural background, and environment will influence the way that he/she
addresses the patient’s self-care requisites (Hartweg, 1991).
In this study, nursing agency involves the knowledge base of the nurse
practitioner regarding the relationship of estrogen therapy and cardiovascular
8
risk. The implications of this study will add to the knowledge base and serve
to provide additional evidence regarding estrogen in relation to coronary
artery disease.
Nursing System. The sixth concept in Orem’s theory is nursing system,
defined as the actions and interactions between nurses and patients in nursing
practice. Nursing systems are divided into three separate systems, (a) the
wholly compensatory system in which the nurse performs all self-care for the
patient, (b) the partly compensatory system in which the nurse and the patient
share self-care responsibility, (c) the supportive-educative system in which
the patient is responsible for his/her own self-care and the nurse provides
guidance and education regarding self-care activity (Orem, 1995). Utilizing
information from this study, the nurse practitioner functions in the
supportive/educative system, providing information to postmenopausal
patients regarding the cardiovascular benefit of estrogen therapy.
Statement of Purpose
It has been recommended in the literature that further research into the
relationship between postmenopausal estrogen therapy and cardiovascular
disease be conducted (Wenger et al., 1993). The purpose of this current study
was to analyze the relationship between estrogen therapy and presence of
CAD in postmenopausal women undergoing cardiac angiography.
9
Consideration was given to the coexisting cardiovascular risk factors of
smoking, obesity, hypertension, diabetes mellitus, and prior history of CAD.
Assumptions
The assumptions of this study were as follows:
• ■ The onset of cardiovascular disease can be delayed or prevented with
estrogen therapy.
2. The women being studied are postmenopausal.
3. The women being studied know whether or not they have been
taking estrogen therapy.
4. Cardiac angiography results were accurately documented in the
patients’ charts.
5. Survey data were obtained in a consistent manner.
Limitations
The limitations of this study were as follows:
1. The sample studied was from the population of a cardiac
catheterization laboratory and, therefore, a higher incidence of cardiovascular
disease may be present in comparison to the general population.
2. The study was performed retrospectively and, therefore, the accuracy
of the study data will depend upon the accuracy of the initial documentation.
10
3. Only subjects receiving treatment for hypertension were classified as
being hypertensive in this study and, therefore, undiagnosed hypertensive
subjects were not accounted for in this study.
4. Only subjects receiving treatment for diabetes mellitus were
classified as diabetic in this study and, therefore, undiagnosed diabetics were
not accounted for in this study.
5. Results of this study were limited to patients within one hospital
cardiac catheterization laboratory and, therefore, they may not be
generalizable to other populations.
6. This study did not account for other independent risk factors for
CAD that may be present such as homocystinemia, elevated lipoprotein (a), or
elevated apolipoprotein B.
Definition of Terms
The terms used in this study were as follows:
1 Cardiac angiography involves the injection of a contrast agent into
the ostia of either the left main or right coronary arteries in order to determine
the percentage of coronary artery narrowing at a site of obstruction, if any
(Barry, 1996).
2. Cardiovascular disease (CVD) is a general diagnostic category that
consists of several disease entities affecting the cardiovascular system.
11
Included in this category are coronary artery disease, peripheral vascular
disease, and structural heart dise:ase (Friedewald, 1996).
3. Coronary artery disease (CAD), a form of cardiovascular disease, is
arteriosclerosis of the coronary arteries that involves the formation of lipid-
rich, thickened, and hardened lesions on the interior coronary artery wall.
These lesions may rupture or become large enough to obstruct the entire
artery lumen, leading to tissue ischemia and necrosis, clinically seen as
myocardial infarction (Ross, 1996). Risk factors for the development of CAD
include hyperlipidemia, decreased HDL-C level, smoking, diabetes mellitus,
hypertension, obesity, physical inactivity, and genetic predisposition (Ross,
1996).
4. Hormone therapy (HT) is defined as noncontraceptive estrogen use
during the menopause (Greendale & Judd, 1995). Estrogen may be
administered in one of two ways: (a) unopposed, in which only estrogen is
given in either oral or transdermal form, or (b) given with progestin on a daily
or cyclic basis (Greendale & Judd).
5. Hyperlipidemia is defined as an abnormally elevated total serum
cholesterol and/or triglyceride levels (Witzum & Steinberg, 1996). The total
cholesterol is divided into high density lipoprotein (HDL-C), which serves to
remove excess cholesterol and decrease lipid deposits on arterial walls, and
12
low density lipoprotein (LDL-C), which deposits on arterial walls leading to
atheroma formation (Witzum & Steinberg).
6. Menopause is the cessation of ovarian function that leads to
permanent amenorrhea, occurring at an average age of 50 years (Greendale &
Judd, 1995).
Summary
Cardiovascular disease (CVD) is the leading cause of mortality in
women (AHA, 1999). Although the prevalence of CVD is higher in men,
women are more likely to die from CVD than men (AHA). Gaps in the
diagnosis and treatment of CVD in women have been identified which
contribute to the poorer prognosis in women (Wenger et al., 1993). Women
have also been underrepresented in research regarding CVD, leading to
insufficient information concerning prevention, diagnosis, and treatment of
CVD in women (Wenger et al., 1993). Estrogen has been shown to have a
cardioprotective effect in the development of CVD in women, with further
research into this area being recommended (Nabulsi et al., 1993).
The purpose of this study was to perform a retrospective analysis of
estrogen use in postmenopausal women over 50 years of age with
angiographic evidence of CAD. Assumptions and limitations of this study
13
were expressed and definitions of the terms used within the study were
provided.
The theoretical framework used for this study was Dorthea Orem’s
Self-Care Theory. Estrogen therapy was identified as a health deviation self-
care requisite of the postmenopausal woman. This was followed by a
discussion of the role of the nurse practitioner within a supportive-educative
nursing system.
14
Chapter 2
Review of Literature
This chapter provides a review of the current literature concerning the
role of hormone therapy in the prevention of cardiovascular disease (CVD).
The differences in morbidity, mortality, and risk factor development
between men and women are discussed. The physiologic consequences of
menopause, means of hormone therapy, and the role of hormone therapy as
primary and secondary prevention for CVD are reviewed.
Cardiovascular Disease in Women
Cardiovascular disease is a major public health concern in older
women, with costs of CVD and stroke in both men and women exceeding
$250 billion in 1997 (AHA, 1999). Although mortality rates for CVD have
decreased over the past few decades, the rate of decline is less for women
than men (Mosca et al., 1997). CVD has reached an epidemic status in
women. It ranks first among all disease categories of hospital discharges for
women (Mosca et al.), with 2.5 million women being hospitalized each year
for CVD (Wenger et al., 1993).
Mortality. Cardiovascular disease is the leading killer of women m the
United States, claiming 500,000 lives per year (AHA, 1999). One out of
every two women’s deaths is from CVD, a stark comparison to the one out
15
of 27 for breast cancer. A disconcerting finding of the Framingham Heart
Study was that two-thirds of the sudden deaths due to CVD in women
occurred in women having no symptoms of disease (Mosca et al.).
Ethnic differences in CVD deaths have also been identified (Mosca et
al., 1997). Although the overall death rates for CVD are higher in blacks than
whites, black women have a 34% higher mortality rate than white women; in
comparison, black men have only a 5% higher death rate than white men.
Mortality rates for CVD are lower in Mexican-American men than white
men, however, there is no mortality difference between Mexican-American
women and white women.
An unequal gender mortality rate is also observed with
revascularization procedures following myocardial infarction (Mosca et al.,
1997). The Global Utilization of Streptokinase and TPA for Occluded
Arteries (GUSTO-1) study showed the 30-day mortality rate in women to be
double that of men (Mosca et al.). With regard to percutaneous transluminal
coronary angioplasty (PTCA), the long term prognosis was equal in women
and men, however, intraprocedural mortality was three times higher in
women.
Morbidity. A number of factors affecting morbidity from CVD have
been identified (Wenger et al., 1993). It has been shown that women
16
undergo less aggressive and intensive evaluation for CVD than men, leading
to fewer revascularization procedures such as PTCA and coronary artery
bypass grafting. Women who undergo these procedures are typically at a
more advanced stage of disease. Additionally, women have smaller coronary
artery size than men, which further complicates revascularization procedures
(Wenger et al.). The presentation of women with MI differs from men, with
women being more likely to have atypical symptoms such as epigastric pain,
nausea, and fatigue than men (Mosca et al., 1997).
Risk factors. The risk factors for CVD are similar for both women and
men (Mosca et al., 1997). However, certain gender differences regarding
some of these risk factors have been identified (Mosca et al.). Following is a
discussion of these risk factors and how they differ for women.
1. Smoking is the leading preventable cause for CVD, producing a
two to four-fold elevation in risk for both women and men. In the United
States, an overall decline in cigarette smoking has been observed, however,
the rate of smoking cessation in women has shown a slower decline than in
men.
2. Elevated total serum cholesterol and LDL-C are risk factors for
both women and men. Decreased HDL-C has also been shown to be a
17
predictor of CVD morbidity and mortality for both sexes, however, it has
been found to be a stronger predictor for women than men.
3. Both systolic and diastolic hypertension have been found to have a
strong association with CVD in men and women. Isolated systolic
hypertension is of particular concern in elderly women, with a prevalence of
30% in women over 65 years of age.
4. Persons with Type 1 or Type 2 diabetes have a two-fold higher
incidence of myocardial infarction in comparison to nondiabetics, with
diabetic women developing ischemic heart disease at a higher rate than
diabetic men (Ross, 1996). A contributing factor to this increase in risk is the
pattern of low HDL cholesterol, high triglycerides, and insulin resistance
seen in those with diabetes (Sacks, 1995).
5. Data from the Framingham Heart Study gave evidence of a higher
rate of recurrent infarction and heart failure in women following MI
(Wenger, 1995). In the Framingham study, reinfarction following MI
occurred within the first year in 40% of women, in comparison to 13 /o of
men.
Menopause
Menopause can be defined as the cessation of ovarian function which
leads to permanent amenorrhea (Greendale & Judd, 1995). Twelve months
18
of amenorrhea is a significant indicator of the cessation of ovarian function.
The average age of menopause is 50 years (Greendale & Judd). Following
is
a discussion of the physiologic consequences of menopause for the
cardiovascular system, as well as a discussion of the methods of hormone
therapy.
Physiologic consequences. The most profound physiologic
consequence of menopause is upon serum lipid levels, with the average total
cholesterol level in postmenopausal women exceeding the average total
cholesterol level in men (Murabito, 1995). Postmenopausal women have
been found to have higher total cholesterol, LDL cholesterol, and
triglyceride levels than their premenopausal counterparts (Matthews et al.,
1989). In terms of cholesterol, HDL-C is the strongest predictor of CVD
risk, postmenopausal women have been found to have significantly lower
levels of HDL-C in comparison to premenopausal women (Matthews et al.,
1989).
Method of hormone therapy, Estrogen therapy is defined as
noncontraceptive estrogen use in the menopause (Greendale & Judd, 1995).
There are primarily two methods of estrogen therapy, (a) unopposed, which
is estrogen given alone on a daily basis, and (b) estrogen with progestin,
given as a fixed daily dose or on a cyclic basis (Greendale & Judd). The
19
following is a discussion of each method and the risks and advantages of
each.
Administering estrogen on a continuous or cyclic basis, is a method
referred to as unopposed estrogen therapy (Greendale & Judd, 1995). This
method of treatment is preferred for women without an intact uterus, since
estrogen alone confers a high risk of endometrial hyperplasia (Greendale &
Judd). Women with an intact uterus who develop intolerable side effects to
progestin may also be considered for this type of therapy, however,
surveillance biopsies may be required in order to monitor for the
development of endometrial hyperplasia (Greendale & Judd). The most
commonly prescribed form of estrogen in the United States is conjugated
equine estrogen (CEE) at a dose of 0.625mg per day (Greendale & Judd).
Transdermal preparations are available as well, with comparable
effectiveness in menopausal symptom relief and osteoporosis prevention.
The effectiveness of transdermal estrogen as compared to oral therapy in the
prevention of cardiovascular disease has not been demonstrated at this time
(Greendale & Judd).
Combination therapy with CEE 0.625mg and medroxyprogesterone
2.5mg to 5mg administered daily or on a cyclic basis is the next method of
hormone therapy (Greendale & Judd, 1995). This is the therapy of choice for
20
women with an intact uterus as it reduces the risk of endometrial
hyperplasia. Progesterone confers no additional benefit in women without a
uterus (Greendale & Judd). Continuous regimens may be preferred by some
women m that they minimize the undesirable side effects associated with
progestins such as headache, bloating, cramping, and vaginal bleeding
(Greendale & Judd).
Role of Estrogen in the Prevention of CVD
The relationship between menopause, estrogen, and CVD has been a
subject of interest since the early decades of this century (Barrett-Connor &
Bush, 1991). The earliest studies in the 1930s observed differences in the
prevalence of CVD between older and younger subjects, followed by animal
experiments studying the relationship between estrogen and atherosclerosis
(Barrett-Connor & Bush). It has been observed in the literature that CVD
risk is substantially reduced in estrogen users, who have a 50% lower risk
than nonusers (Barrett-Connor & Bush). However, this statement is not
without controversy, with conflicting results being noted in the Framingham
Heart Study, which has shown a statistically significant increase in CVD
mortality among estrogen users (Wilson et al., 1985). Another source of
controversy is the criticism that observational studies of estrogen and CVD
are subject to a certain amount of selection bias (Matthews et al., 1995). A
21
study was performed by Matthews et al. in order to determine if
postmenopausal women being recommended for hormone therapy had a
better cardiovascular risk profile than nonusers. The study included an initial
sample of 541 premenopausal women who were evaluated for
cardiovascular risk factors and psychosocial factors. After an 8 year period,
355 of these women had become postmenopausal, and 157 of them reported
estrogen use. The premenopausal characteristics between users of estrogen
therapy and nonusers were then compared. The results showed that estrogen
users were better educated; had higher levels of HDL-C, physical activity
and alcohol use; and had lower levels of LDL-C, systolic and diastolic blood
pressure, and weight than nonusers (Matthews et al.).
The role of estrogen and CVD prevention continues to be a strong
topic of interest, with continuing research into the employment of estrogen
as a means of both primary and secondary prevention in low and high risk
individuals (Barrett-Connor & Bush, 1991). Also of interest are the
differences in the reduction of CVD risk factors between unopposed
estrogen regimens and combination estrogen/progestin regimens (Barrett-
Connor & Bush). Current studies regarding estrogen’s mechanisms of action
and its role as a primary and secondary prevention agent, as well as studies
22
regarding the differences between unopposed estrogen and
estrogen/progestin regimens, will be discussed next.
Mechanisms of action.. The effects of estrogen upon serum lipid levels
has been the most promising finding in the literature. Research into the
effects upon other CVD risks such as hemostatic factors, carbohydrate
metabolism, and blood pressure are beginning to emerge (Barrett-Connor &
Bush, 1991).
Orally administered estrogen affects lipid metabolism in several ways
(Guetta & Cannon, 1996). Estrogen reduces LDL cholesterol by accelerating
the conversion of hepatic cholesterol to bile acids and increasing the
expression of LDL receptors upon cell surfaces. This leads to increased
clearance. HDL cholesterol is increased by an enhanced production of
apolipoprotein A-l and a decrease in hepatic lipase activity. These actions
are dependent upon the absorption of estrogen from the gut, rendering
transdermal estrogen replacement less effective than oral estrogen in terms
of serum lipid alterations (Guetta & Cannon).
A number of studies involving estrogen replacement and favorable
alterations in lipid profiles have been performed. Bush et al. (1987) followed
2270 postmenopausal women in the Lipid Research Clinics Prevalence
Study. After an 8.5 year follow-up estrogen users had significantly (p <
23
0.05) higher HDL-C and triglyceride levels and significantly lower LDL-C
levels than nonusers. Matthews et al. (1989) performed a 5 year study of 541
premenopausal women making a transition into menopause in order to
determine changes in CVD risk factors. It was found that after menopause,
women taking estrogen therapy had significantly (p < 0.05) higher levels of
triglycerides and apolipoprotein A-l than nonusers. Estrogen users also had
lower levels of LDL cholesterol and higher levels of HDL cholesterol than
nonusers, but these results were not found to be statistically significant
(Matthews et al.).
In addition to serum lipoproteins, estrogen has been identified as
having a relationship to other CVD risk factors. Nabulsi et al. (1993)
performed a cross sectional analysis of the data from the Atherosclerosis
Risk in Communities study. A sample of 4958 postmenopausal women were
divided into one of four groups: (a) current users of estrogen, (b) current
users of estrogen and progestin, (c) nonusers who formerly used hormones,
(d) nonusers who had never used hormones. The factors analyzed included
serum lipoprotein levels, hemostatic factors, carbohydrate metabolism, and
blood pressure. The study had two main hypotheses: that there would be
significant differences in risk factors between users of hormone therapy and
nonusers, and that there would be significant differences between those
24
using unopposed estrogen therapy and those using combination therapy. The
results showed that unopposed estrogen users had significantly (p< 0.001)
higher levels of triglycerides than both nonusers and users of combined
therapy. Users of unopposed estrogen and combination therapy had similar
levels of HDL cholestreol, both being significantly (p < 0.001) higher than
nonusers. LDL cholesterol levels were similar in both groups of estrogen
users, and were significantly (p < 0.05) lower than the levels of nonusers.
Mean fibrinogen levels were similar in both groups of estrogen users, and
were significantly (p < 0.001) lower than in nonusers. Similar levels of
serum glucose were also found in both estrogen replacement groups, with
significantly (p < 0.001) lower levels than nonusers. No significant
differences in systolic or diastolic blood pressure were observed between
any of the groups (Nabulsi et al.).
Primary Prevention. A number of studies regarding the use of both
unopposed estrogen and estrogen/progestin in the prevention of CVD risk
have been published. The Postmenopausal Estrogen/Progestin Interventions
(PEPI) Trial (Writing Group, 1995) studied unopposed estrogen and
estrogen/progestin regimens as primary prevention for CVD risk factors in
healthy women. PEPI was a 3 year, multicenter, randomized, double-blind,
placebo controlled trial of 875 postmenopausal women with no evidence of
25
cardiovascular disease. The women were divided into three treatment
groups: placebo, unopposed estrogen, and estrogen/progestin. The results
showed that the women in both active treatment groups had significantly
higher HDL cholesterol levels than the placebo group, with those on
unopposed estrogen having a significantly higher HDL cholesterol than
those receiving combination therapy. LDL cholesterol levels were
significantly lower in both active treatment groups than in the placebo
group. Triglycerides were significantly higher in both active treatment
groups in comparison to placebo treated women. No significant differences
in blood pressure or glucose and insulin were observed between any of the
groups. Placebo subjects had significantly higher levels of fibrinogen than
treatment groups, as well as a significantly higher weight gain than treatment
groups. The PEPI researchers concluded that unopposed estrogen was the
treatment of choice in order to increase HDL cholesterol in women without a
uterus, and estrogen with cyclic medroxyprogesterone was the treatment of
choice in women with an intact uterus (Writing Group, 1995).
Grodstein et al. (1996) also conducted a study in order to compare the
effectiveness of estrogen/progestin and unopposed estrogen regimens in the
prevention of CVD. These researchers followed the subjects (n = 59,337) of
the Nurses’ Health Study who were ages 30 to 55 at baseline, for a period of
26
16 years. They found that the risk of CVD in women who used
estrogen/progestin regimens was significantly lower than among nonusers,
and that this reduction was similar to the risk reduction conferred by
estrogen alone (Grodstein et al.).
Secondary Prevention. The Heart and Estrogen/Progestin
Replacement Study (HERS) looked at the effects of unopposed estrogen and
estrogen/progestin regimens as prevention for recurrent CVD events in
women with pre-existing CVD (Hulley et al., 1998). HERS was a
randomized, blinded, placebo controlled trial involving 2763 women with
coronary artery disease. The women were divided into two groups: one
group given placebo and another given CEE with progesterone. The women
were then monitored over a 4 year period for the development of nonfatal
myocardial infarction, death due to CVD, coronary revascularization
procedures, congestive heart failure, unstable angina, stroke, and peripheral
vascular disease. The researchers found no significant differences between
the two groups in any of the above outcomes, however, a significantly
higher incidence of venous thromboembolic events and gallbladder disease
was seen in the hormone group. From these data, it was recommended that
hormone therapy not be initiated as a means of secondary prevention for
recurrent CVD, however it would be appropriate for women receiving
27
therapy pnor to a CVD event to continue therapy after the event (Hulley et
al.).
The Women’s Health Initiative (WHI), recently initiated by the
National Institute of Health, is the largest United Sates prevention study of
its kind. It will involve three major components: (a) randomized controlled
clinical trials of approaches to prevention coronary disease, breast cancer,
and hip fractures in women, (b) observational studies to identify predictors
of disease, and (c) community study of approaches to identify healthy
behavior development (Rossouw et al., 1995). Approximately 63,000
women will be enrolled in clinical trials which will be performed at 40
centers across the United States. Ten of these centers focus on the
recruitment of minority populations. Hormone therapy will be represented in
one of the clinical trials, with the primary outcome of the trial being
coronary artery disease. Results of the WHI will be available by the year
2007 (Rossouw et al., 1995).
Summary
This chapter provided an ov<'erview of the role of estrogen in the
prevention of CVD. Examples of the differences in cardiovascular morbidity
and mortality between men and women were
provided. Physiologic
consequences of menopause were also discussed, as well as methods of
28
hormone therapy. A discussion of the results of various studies regarding the
effects of estrogen upon the development of CVD, and the role of estrogen
in primary prevention of CVD and in the prevention of recunent CVD
events was given. As indicated by this literature review, further research into
the relationship between estrogen therapy and CVD is needed.
29
Chapter 3
Methodology
The purpose of this study was to analyze the relationship between
postmenopausal estrogen replacement and coronary artery disease (CAD),
giving consideration to the other coexisting CAD risk factors of smoking,
hypertension, diabetes mellitus, obesity, and history of CAD. This chapter
provides a description of the methodology used to obtain and analyze data.
A discussion of the research hypothesis, research design, instrumentation,
sample, setting, and procedure are included in this chapter. Operational
definitions are provided in this chapter. Protection of human rights is
discussed. The pilot study and method of data analysis are also described.
Hypothesis
There was a statistically significant inverse relationship between
estrogen use in postmenopausal women and the presence of CAD.
Operational Definitions
The following terms are defined as they were used in this study.
1. Coronary artery disease is the angiographic presence of one or more
lesions with a 50% or greater obstruction of coronary vessel lumen m a
symptomatic individual. All angiography results were obtained and
interpreted by board certified cardiologists.
30
2. Diabetes mellitus was present when a subject was taking oral
antihyperglycemic agents, oral insulin sensitizing agents, or insulin via daily
injections or an insulin pump.
3. Estrogen therapy was the use of either unopposed estrogen at a dose
of 0.625mg or greater on a daily basis, or combined estrogen (0.625mg or
greater) and progesterone 2.5mg or greater on a daily or cyclic basis.
Transdermal preparations were not considered as part of the definition of
estrogen replacement therapy in this study.
4. A history of CAD was present in a subject who had undergone
previous revascularization procedures (percutaneous transluminal coronary
angioplasty [PTCA], coronary artery bypass grafting) or who had been
diagnosed with a myocardial infarction prior to the current admission for
cardiac catheterization.
5. Hypertension was present when a subject was taking
antihypertensive medications at the time of the study.
6. Obesity was defined as having a body mass index (BMI) greater
than 28 kilograms per meters squared (kg/m2). The BMI was obtained by
pressed in kilograms by the height expressed
dividing the subject’s weight ex]
in meters squared.
31
7. A postmenopausal woman was one who has been amennorheic for
12 months or longer. Women who had undergone surgical procedures
leading to permanent amennorhea, such as bilateral oophrectomy, were also
enrolled in this study if those procedures had been performed more than
twelve months prior to the study.
8. Smoking was defined as the daily use of cigarettes or any other
tobacco products, such as cigars or pipes.
Setting
The setting for this study was a cardiac catheterization laboratory,
located within a 487 bed acute care facility in northwestern Pennsylvania.
The laboratory consisted of three catheterization suites and an eight bed
holding/recovery area. The laboratory averages over a total of 1,500 cardiac
catheterizations per year.
Sample
The sample of 36 subjects was obtained over a 4 week period from
February 21 through March 21,2000, from the population of women
presenting to the cardiac catheterization laboratory for left heart
catheterization (LHC). Inclusion criteria were that the subjects must be 5.0
years of age or older and amennorheic for 12 months or longer. During the
designated time frame, 39 surveys were completed. Three surveys were
32
discarded because they did not meet the inclusion criteria, for a final sample
size of 36. Of the 36 useable surveys, 100% of the subjects were 50 years of
age or older and at least 12 months postmenopausal. Of the 36 subjects, 9
were current estrogen users (25%), and 27 were nonusers (75%). All of the 9
subjects currently using estrogen had been receiving therapy for 6 months or
longer. Of the 27 nonusers, 5 subjects (18.5%) had taken estrogen in the
past, while the remaining 22 subjects (81.5%) had never taken estrogen. All
of the 5 subjects who were past users of estrogen had discontinued therapy
greater than 3 years ago.
Pilot Study
A sample of 16 charts from women 50 years of age and older who
underwent LHC was selected for the pilot study. These charts were reviewed
and data regarding estrogen therapy, smoking habits, hypertension, BMI,
and presence of cardiovascular disease were recorded and placed on a
contingency table. Chi-square was chosen as the method of data analysis
because the data obtained were nominal. A Chi-square analysis with a
statistically significant level of p=<0.05 was then performed for each risk
factor and the development of CAD. Pilot study results were reported in
aggregate and according to presence of each risk factor. Expected values
were calculated from the actual values. Significant differences were found
33
between the risk factors of smoking, hypertension, and obesity in the
development of CAD. A Chi-square analysis was also performed to
determine differences between estrogen users and nonusers in terms of the
development of CAD. No significant difference in the development of CAD
was found between the estrogen users and nonusers. This finding was
contradictory to other findings in the literature regarding estrogen and CAD.
The small sample size was a consideration, as was the accuracy of the
information found in the charts.
It was decided that subject interviews regarding estrogen therapy and
the other risk factors being studied would serve to increase the accuracy of
the data. It was also decided that questions regarding the duration of
estrogen replacement therapy, history of CAD, and diabetes mellitus would
be added to the survey in order to provide further clarification of the role of
estrogen in CAD development. No changes were made to the survey items
that addressed smoking, hypertension, and obesity.
Research Design
This study utilized a retrospective descriptive research desrgn. The
independent variables studied were postmenopausal estrogen replacement,
smoking habits, hypertension, obesity, diabetes mellitus, and history of
34
CAD. The dependent variable was the presence of CAD
to obtain data were subject interview and patient chart review.
Instrumentation
A researcher-designed survey was used as the research tool (Appendix
A). The survey was formatted for the use with an automatic survey scanning
machine. Questions 1 and 2 were used as criteria for subject eligibility to
participate in the study, determining subject age (equal to or greater than 50)
and menopausal status (no menstrual cycle for 12 months or longer). A
“yes” response was required for both items in order to be included in the
study.
Questions 3, 4, 5, and 6 classified estrogen use. Question 3 asked
about current estrogen use. Question 4 asked about the duration of current
estrogen therapy. Questions 5 and 6 were directed to the 27 subjects with a
“no” response to question 3 in order to determine past use of estrogen and
the amount of time elapsed since the cessation of therapy.
The risk factor of obesity was indirectly addressed with questions 7
and 8, which asked for the subject’s height in inches and weigh
kilograms. These values were used to calculate a body mass index (BMI) for
each subject. A value of 28kg/m! or greater was considered by the researcher
to be obese. Height and weight were omitted on one survey from a subject
35
Who had never used estrogen. A BMI eould not be calculated for this
subject, reducing the number of “never”
estrogen users to 21 for this
question only. The other responses in this particular survey were included in
the other data analyses. Question 9 concerned smoking habits at the time of
hospital admission. Question 10 addressed hypertensive status; only subjects
receiving antihypertensive medications were classified as being
hypertensive. Question 11 concerned the presence of diabetes mellitus; only
subjects receiving antihyperglycemic agents, insulin sensitizing agents, or
insulin by daily injection or insulin pump were classified as being diabetic.
Question 12 sought a history of CAD. Question 13 addressed the presence of
significant coronary artery lesions found during the subject’s
catheterizations.
Inter-rater Reliability
This survey was administered by 4 registered nurses instructed on the
study’s purpose, design, method of data collection, and protection of patient
confidentiality. In order to determine inter-rater reliability, a case study of a
fictitious patient (Appendix B) was given to the nurses, who were then asked
to fill out the survey using data from the case study. Agreement on 12 of
answer key statements was required for the nurses to be considered rehab
36
to collect data. All of the 4 nurses responded correctly on greater than 12
items on the sample survey.
Procedure
Upon arrival to the lab, each female patient 50 years of age or older
scheduled for LHC was approached by the researcher or research assistants.
The potential subjects were informed of the study’s purpose and the
information that would be required from them. They were then asked if they
would be willing to participate in the study. All research assistants followed
a standardized outline for obtaining oral informed consent (Appendix C).
Agreement to participate in the study was considered informed consent.
After consent was obtained, the researcher or research assistants
obtained subject data using the researcher-designed survey. Survey data
were collected via subject interview and chart review. Data obtained through
subject interview included postmenopausal status, estrogen use, smoking
habits, the presence of hypertension, diabetes mellitus, and history of CAD.
Chart review was utilized to obtain data regarding the subject s age, height
and weight and cardiac angiography results.
After the interview, the subjects underwent left heart catheterizatrons,
which were performed and interpreted by board cerufied cardiologists.
When the catheterizations were completed, the subject’s record was agam
37
reviewed to obtain coronary angiography results. These results were then
entered on the survey; the completed surveys were placed in a secured area.
Protection of Human Rights
All subjects entered into the study were informed of the purpose of the
study and of the information that would be obtained from them. All subjects
were ensured anonymity. All subjects were given the opportunity to decline
to participate in the study. Verbal agreement to participate in the study was
considered informed consent. Neither names nor medical record numbers
were placed on the survey. The surveys will remain secured for a period of 3
years at which time they will be destroyed. Only grouped data were
reported. Permission to perform the study was obtained from the medical
director of the cardiac catheterization laboratory, and the department team
leader (Appendix D), and the institution’s review board (Appendix E).
Data analysis
The responses to the survey were analyzed using descriptive and
inferential statistics, and nonparametric testing. The AutoData® Survey
software was used to tabulate the responses to the survey. The Statistical
Package for the Social Sciences (SPSS®) Base
1988 was utilized for data analysis.
8.0 for Windows, copyright
38
The results of the study were reported in aggregate according to types
of estrogen users (current use, past use, never used), presence of each risk
factor, and presence of CAD on cardiac catheterization. The data presented
were nominal (categorical) and dichotomous, and were analyzed using
descriptive and inferential statistics and nonparametric techniques. All data
were placed into contingency tables of varying size for the determination of
independence between each type of estrogen user groups, and for the
measurement of relationships between presence of each risk factor, estrogen
use and CAD. Because some of the expected cell frequencies had values less
than 5, a Fisher’s exact test of probability was used to determine
independence between estrogen user groups, with expected responses being
derived from the actual numbers.
As the contingency tables were larger than 2 x 2, a Cramer s V (F)
was selected to measure relationships. All percentages were calculated to
two decimal points and rounded to one decimal point. If a value after the
decimal point was greater than or equal to .05, it was rounded to the next
highest number. A level of significance ofp=0.05 was established for all
calculations. Categories for the V value (indicating relationship strength)
were obtained from Munro and Page (1986) and classified as follows: (a)
39
0.00-0.25 little if any, (b) 0 26-9.49 low, (c) 0.50-0.69 moderate, (d) 0.70-
0.89 high, (e) 0.90-1.0 very high.
Subjects were initially classified into two groups of estrogen users,
current users and nonusers. After examination of the data from questions 3
through 6 of the survey, the original two groups were reclassified into three
groups. The group of current users stayed the same, however, nonusers were
divided into two separate groups: those who had used estrogen in the past
(greater than 3 years), and those who had never used estrogen. After the
subjects were classified into estrogen user groups, tests for independence
among the groups in terms of risk factors were performed using Fisher’s
exact test. The presence of each risk factor was calculated for each
classification of estrogen user.
The next step of data analysis was the evaluation of relationships
between estrogen use and presence of CAD, and risk factors and presence of
CAD within each group of estrogen users. After the Cramer s V for the
relationship between estrogen use and CAD was
obtained, the relationship
between presence of risk factors and presence of CAD for each group of
estrogen user was performed. A contmgency table was constructed for each
,fCAD and presence or absence of each of
according to presence or absence o
40
the five risk factors. Percentages for each value in the table were calculated
by dividing the number of subjects with (or without) each risk factor by the
total amount of subjects with (or without) CAD. This percentage reflected
the prevalence of each risk factor among subjects with or without CAD. In
addition to the analysis of relationship between each risk factor and CAD,
the data were also examined for trends in the prevalence of particular risk
factors in those with and without CAD.
Summary
The purpose of this study was to analyze the relationship between
postmenopausal estrogen therapy and CAD, giving consideration to the
other coexisting CAD risk factors of smoking, hypertension, diabetes
mellitus, obesity, and history of CAD. This chapter provided a description of
the methodology used to perform this analysis, including research design,
protection of human rights, hypothesis, instrumentation, setting, sample and
procedure. Operational definitions for this study were provided, and the
method of data analysis in the pilot study was discussed.
41
Chapter 4
Results
The purpose of this study was to analyze the relationship between
postmenopausal estrogen therapy and the presence of coronary artery disease
(CAD), giving consideration to five other possible coexisting CAD risk
factors of obesity, hypertension, cigarette smoking, diabetes mellitus, and
previous history of CAD. It was hypothesized that there was a statistically
significant inverse relationship between CAD and estrogen use in
postmenopausal women. The data for the study were obtained using a
researcher-designed survey (Appendix A) that entailed a subject interview
and review of the subject’s medical record. The results of this survey are
presented in this chapter.
Tests of Independence
The subjects were classified into groups of current users of estrogen
(n==9), past users of estrogen (n=5), and those who had never used estrogen
(n=22). A Fisher’s exact test was used to determine independence am g
groups of estrogen users in terms of presence of CAD and presence of the
risk factors of obesity, smoking, hypertension, diabetes melhtus, and history
of CAD.
42
Presence of CAD. The data regarding estrogen use and presence of
CAD are presented m Table 1. The lowest rate of CAD was observed in the
group of past estrogen users, with the highest rate being observed in the
group of current estrogen users. A Fisher’s exact test showed that when
compared to expected, there were no statistically significant differences
among the three groups of estrogen users and presence of CAD.
Table 1
Estrogen Use and Presence of CAD
Estrogen Use
CAD
Current
(n=9)
Total
(N=36)
n
(%)
n
(%)
Never
(n=22)
Past
(n=5)
n
(%)
n
(%)
Yes
26 (72.2%)
7 (77.8%) 2 (40.0%) 17(77.3%)
No
10 (27.8%)
2 (22.2%) 3 (60.0%)
5(22.7%)
Obesity. Of the 35 subjects with a response to this question, 23
(65.7%) were classified as obese. Hie lowest incidence of obesity (20%) was
43
noted in the group of past estrogen users. A Fisher’s exact test showed no
statistically significant differences among the three groups of estrogen users
in the presence of obesity. The data on obesity and estrogen use are
summarized in Table 2.
Table 2
Estrogen Use and Obesity
Estrogen Use
Obesity
Total
(N=35)
n
(%)
•
n
Never
(n=21)
Past
(n=5)
Current
(n=9)
(%)
n
(%)
n
(%)
Yes
23 (65.7%)
7 (77.8%)
No
12 (34.3%)
2 (22.2%) 4 (80.0%) 6(28.6%)
1 (20.0%) 15(71.4%)
Note, One survey was omitted from “never•” users due to incomplete
information for this item.
Smoking. Of the 36 subjects, 6 were smokers (16.7%), and 30 were
nonsmokers (83.3%) at the time of admission. Subjects who had used
estrogen in the past had the highest smoking rates (20%), with the lowest
rates (11.1%) being observed in the current estrogen users. The data for
44
smoking and estrogen use are presented in Table 3. A Fisher’s exact test
showed no statistically significant differences in smoking among the three
groups of estrogen users.
Table 3
Estrogen Use and Smoking
Estrogen Use
Smoking
Total
(N=36)
n
Yes
No
Current
(n=9)
(%)
6 (16.7%) •
30 (83.3%)
n
Never
(n=22)
Past
(n=5)
(%)
n
(%)
n
(%)
1 (11.1%)
1 (20.0%) 4(18.2%)
8 (88.9%)
4(80.0%) 18(81.8%)
Hypertension. Of the 36 subjects, 28 (77.8%) were classified as
hypertensive and 8 (22.2%) were classified as nonhypertensive. The rates of
hypertension were similar between the group who had never used estrogen
(81.8%) and the group of past users (80%). Current estrogen users had the
lowest incidence (66.7%) of hypertension (Table 4). A Fisher’s exact test
showed no statistically significant differences in presence of hypertension
among the three groups of estrogen users.
45
Table 4
Estrogen Use and Hypertension
Estrogen Use
Hypertension
Total
(N=36)
n
Current
01=9)
(%)
n
Never
(n=22)
Past
(n=5)
(%) n
(%)
n
(%)
Yes
28 (77.8%)
6 (66.7%) 4 (80.0%)
18(81.8%)
No
8 (22.2%)
3 (33.3%) 1 (20.0%)
4 (18.2%)
Diabetes. The risk factor of diabetes was classified according to each
group of estrogen users (Table 5). Of the 36 subjects, 7 (19.4%) were
classified as diabetics and 29 (80.6%) were classified as nondiabetics. The
highest incidence of diabetes (27.3%) was observed in the subjects who had
never taken estrogen. The lowest incidence (0%) was in the subjects with a
past use of estrogen. A Fisher’s exact test showed no statistically significant
differences in the incidence of diabetes among the three groups.
History of CAD. Of the 36 subjects, 14 (38.9%) had a history of
CAD, with the highest incidence of prior history in current estrogen users. A
46
Table 5
Estrogen Use and Diabetes
Estrogen Use
Diabetes
Total
(N=36)
n
Current
(n=9)
(%)
n
Past
Never
(n=22)
05)
(%)
n
(%) n
(%)
Yes
7 (19.4%)
1 (11.1%)
0
No
29 (80.6%)
8 (88.9%)
5 (100.0%) 16(72.7%)
(0.0%) 6 (27.3%)
Fisher’s exact test showed no statistically significant difference in CAD
history among the three groups (Table 6).
Relationship and Trend Analysis
After tests of independence were performed, relationships between
estrogen use and presence of CAD, and risk factors and presence of CAD for
each group of estrogen users were analyzed using Cramer s V.
The relationship between estrogen use and presence of CAD was the
first relationship to be summarized (Table 1).
47
Table 6
Estrogen Use and History of CAD
Estrogen Use
History of CAD
Total
(N=36)
n
Current
(n=9)
(%)
n
Past
(n=5)
(%) n
Never
(n=22)
(%)
n
(%)
Yes
14 (38.9%)
4 (44.4%) 2 (40.0%) 8 (36.4%)
No
22 (61.1%)
5 (55.6%) 3 (60.0%) 14 (63.6%)
A Cramer’s V showed a low positive correlation (Y=0,26) between the
variables of estrogen use and CAD, however, this value was not statistically
significant.
Current estrogen users. Two trends were noted within the group of
current estrogen users (n=9). The first was that 100% of the subjects without
CAD (n=2) were nonsmokers. The second was that both of the subjects
without CAD were nondiabetics. Cramer’s V showed little if any positive
relationships between each of the risk factors and presence of CAD. The risk
factor with the strongest relationship to presence of CAD was hypertension,
48
showing a low positive relationship, with a Vvalue of 0.38. The risk factor
with the weakest positive relationship to the presence of recurrent CAD was
history of CAD, with a V value of 0.06. None of the calculated V values
achieved a 0.05 level of significance. These data for the current estrogen
users are summarized in Table 7.
Past estrogen users. For the group of past estrogen users (n=5), two trends
emerged from the data. The first was that all subjects without CAD (n=3)
were nonsmokers. The second trend was that 100% of the subjects with
CAD (n=2) had a history of CAD and 100% of the subjects without CAD
(n=3) did not have a history of CAD. The V values for this group as
calculated by a Cramer’s V ranged from low to high. The Vvalue for the
relationship between diabetes and presence of CAD was not calculated for
this group due to an insufficient amount of data for calculation. The
strongest positive relationship was between the risk factor of history of CAD
and presence of CAD, with a V value of 1.00. This value was significant at
P=0.03. The weakest positive relationship was between obesity and CAD,
with a V value of 0.41. With the exception of CAD history, none of the
remaining rvalues were found to be significant at a level of 0.05. The data
for presence of risk factors and CAD are summarized in Table 8.
49
Table 7
Risk Factors and Presence of CAD in Current Users of Estrogen (N=9)
Presence of CAD
Total
(N=9)
Yes
(n=7)
Risk Factor
n
n
Obesity
Yes
7
5 (71.4%)
2
2 (28.6%)
1
1
No
8
HTN
Yes
No
No
Smoking
Yes
Diabetes
Yes
No
History
Yes
No
V
No
(n=2)
(%)
(%)
n
2 (100.0%)
0.29
0
(0.0%)
(14.3%)
0
(0.0%)
6
(85.7%)
2 (100.0%)
6
4
(57.1%)
2 (100.0%)
3
3
(42.9%)
0
(0.0%)
(14.3%)
0
(0.0%)
1
1
8
6
(85.7%)
4
3
(42.9%)
5
4
(57.1%)
0.19
0.38
0.19
2 (100.0%)
1
(50.0%)
1
(50.0%)
0.06
50
Table 8
Risk Factors and Presence of CAD in Past Users of Estrogen (N=5)
Presence of CAD
Total
(N=5)
Yes
(n=2)
V
No
(n=3)
n
Risk Factor
n
n
Obesity
Yes
1
0
4
2 (100.0%)
2 (66.7%)
1
1 (50.0%)
0
No
4
1 (50.0%)
3 (100.0%)
HTN
Yes
4
1 (50.0%)
3 (100.0%)
No
1
1 (50.0%)
0
(0.0%)
0
0
(0.0%)
0
(0.0%)
5
2 (100.0%)
3 (100.0%)
2
2 (100.0%)
0
3
0
No
Smoking
Yes
Diabetes
Yes
No
History
Yes
No
(%)
(0.0%)
(%)
1 (33.3%)
0.41
(0.0%)
*Note: Insufficient data to calculate V
(0.0%)
0.61
0.61
*
(0.0%)
1.0
3 (100.0%)
51
Never estrogen users. A trend appearing from the data in the group of those
who had never used estrogen (n=22) was that 100% of the subjects without
CAD (n—6) were nonsmokers. The relationships between each risk factor
and presence of CAD were then analyzed for the group of subjects who had
never used estrogen (n—22). The strength of the relationships between risk
factors and presence of CAD within the group of those who had never used
estrogen ranged from little to low. The relationship with the strongest
positive relationship within this group was between obesity and presence of
CAD, with a Vvalue of 0.38. The weakest positive relationship within this
group was between diabetes and presence of CAD, with a V value of 0.15.
None of the calculated K values were found to be significant at the 0.05
level. These data on risk factors and presence of CAD in subjects never
using estrogen can be found in Table 9.
Summary
This chapter has presented the results of a study of postmenopausal
women undergoing left heart catheterization. The subjects (N=36) were
placed into three groups according to estrogen use: current (n=9), past (n=5),
and never (n=22). The results of this study were analyzed using descriptive
and inferential statistics, and nonparametric testing. Fisher’s exact test was
52
Table 9
Bisk Factors and PresencetrfCADin Never Users of Bstrouen (N-m
Presence of CAD
Total
(N=22)
Yes
(n=16)
No
(n=6)
V
Risk Factor
n
n
(%)
n
(%)
Obesity*
Yes
15
12 (75.0%)
3
(60.0%)
No
Smoking
Yes
0.38
6
4 (25.0%)
2 (40.0%)
4
4 (25.0%)
0
(0.0%)
0.29
No
18
12 (75.0%)
6 (100.0%)
HTN
Yes
18
14 (87.5%)
4
(66.7%)
0.24
No
Diabetes**
Yes
No
History**
Yes
No
4
2 (12.5%)
2
(33.3%)
6
5(31.3%)
1
(16.7%)
16
11 (68.8%)
8
7 (43.8%)
1
14
9 (56.3%)
5 (83.3%)
‘Note: Data on one survey insufficient to calculate BMI.
**Note: Percentages >100 due to method o roun g
0.15
5 (83.3%)
(16.7%)
0.25
53
used to determine the mdependence between the three groups of estrogen
users in terms of the presence of CAD and presence of obesity, smoking,
hypertension, diabetes, and CAD history. No statistically significant
differences were found among the three groups of estrogen users in terms of
the presence of CAD. There were no statistically significant differences
between the three groups of estrogen users in the presence of the five risk
factors considered in this study.
After tests for independence were performed, the relationship
between estrogen use and the presence of CAD was analyzed. The
relationships between the presence of each risk factor and the presence of
CAD were analyzed according to each group of estrogen users. A Cramer’s
V was used for relationship analyses. A low positive (PM).26) correlation
between estrogen use and CAD was found, however, this value was not
significant at ^=0.05. The relationship between history of CAD and presence
of CAD in past users of estrogen was positive (7-1.0) and significant at the
0.03 level. The strength of the relationships between risk factors and the
presence of CAD in the remaining groups ranged from little, if any to
moderate, however, none of these values were significant at/? 0.05.
54
Chapter 5
Discussion
This chapter provides a discussion of this study of estrogen use and
presence of coronary artery disease (CAD) in postmenopausal women. The
findings of the study are summarized and then compared to other studies in
the literature. The findings are then related to the theoretical framework used
for this study and relevance of the findings to the nurse practitioner is
discussed. Conclusions and recommendations for further research are also
provided in this chapter.
A researcher-designed survey was administered to postmenopausal
women undergoing left heart catheterization in a cardiac catheterization
laboratory located in an acute care facility in northwestern Pennsylvania.
The subjects were categorized into three groups: current estrogen users, past
estrogen users, and those who had never used estrogen. An analysis of the
risk factors of obesity, smoking, hypertension, diabetes mellitus, and history
of CAD was performed for each group. Data were analyzed using
descriptive statistics and nonparametric tests.
In this study, it was hypothesized that there was an mverse
relationship between estrogen use and the presence of CAD in
postmenopausal women. The hypothesis was rejected. Analy
55
relationship with Cramer’s V demonstrated a low positive correlation
(V=0.26) between estrogen use and presence of CAD, however, this value
was not significant at the 0.05 level. A similarity can be drawn between this
result and the results of the Heart and Estrogen/Progestin Replacement
Study (HERS). In studying estrogen use in postmenopausal subjects with
established CAD, HERS researchers found no significant reduction in
recurrent coronary events in subjects taking estrogen (Hulley et al., 1998).
Although this study did not limit subjects to those with established CAD, the
rates of history of CAD were highest in the group of current estrogen users.
In this study, the overall prevalence of CAD in the entire sample
(N=36) was 72.2%. It was anticipated at the onset of the study that CAD
would be more prevalent in this sample as it was derived from the
population referred to a cardiac catheterization laboratory. The differences in
the presence of CAD among the estrogen using groups were not found to be
statistically significant using a Fisher’s exact test. The lowest incidence of
CAD was in past users of estrogen, all of whom had discontinued estrogen
therapy 3 years ago or longer. The low incidence of CAD in past users m
this study was in contrast to the findings from the Nurses’ Health Study
(Grodstein et al., 1996). In the Nurses’ Health Study, the protective benefit
of estrogen against CAD began to diminish 3 or more years after therapy
56
was stopped. The favorable risk profile observed in this study for past users
of estrogen, who had the lowest rates of obesity, diabetes mellitus, and CAD
history, may provide an explanation for this observation.
Risk factor analysis for the presence of obesity, smoking,
hypertension, diabetes mellitus, and CAD history showed no statistically
significant differences between the three groups of estrogen users. One
pattern of risk factors noted in this study was that current estrogen users had
the lowest rates of smoking and hypertension. Although the past users had
the lowest incidence of diabetes, current users had a lower incidence of
diabetes than those who had never used estrogen. These results can be
compared to a study performed by Matthews et al. (1996) to determine if
estrogen users had a better cardiovascular risk profile than nonusers.
Matthews et al. found that prior to initiating therapy, estrogen users had
lower blood pressure, lower weight, and lower fasting insulin levels than
nonusers. In contrast, estrogen users had the highest rates of obesity in this
study. However, another study performed by Matthews et al. (1989) found
no statistically significant difference in postmenopausal weight gain between
estrogen users and nonusers, nor did estrogen users lose weight after
initiating therapy. Researchers of the Postmenopausal Estrogen/Progestm
57
Interventions (PEPI) trial (Writing group, 1995) also noted that waist-hip
ratio increased over time at a similar rate in users and nonusers of estrogen.
The lower rate of hypertension in the current estrogen users of this
study is unlikely to be related to estrogen use. It was noted in the PEPI trial
that there were no significant differences in systolic or diastolic blood
pressure between estrogen users and nonusers (Writing group, 1995). It is
possible, as noted in Matthews et al. (1996), that estrogen users are more
compliant individuals who are more likely to follow diet and exercise
regimens, both of which would favorable impact blood pressure.
This study also analyzed the relationships between each of the five
risk factors and presence of CAD within each of the estrogen groups. No
statistically significant relationships were found, with the exception of CAD
history and presence of CAD in the past users. A trend that emerged from
the data was that 100% of the subjects without CAD in all groups of
estrogen users were nonsmokers.
Conclusions
Several factors contributing to the rejection of the hypothesis were
identified. One factor that influenced this was the small sample size, which
led to a less than desired number of estrogen users available for analysis.
The small sample size also impacted the calculations. A second factor was
58
that the sample was taken from a population with a higher prevalence of
CAD than the general population. Another possible contributing factor was
that the estrogen users in this study had higher rates of obesity and CAD
history than the past users and never users. It was also noted that the
influence of other CAD risk factors, such as hyperlipidemia, homocystine,
and positive family history, were not included in this study. The combination
of these other risk factors with the risk factors considered in the study may
have had an unidentified impact upon the presence of CAD in the subjects.
Although the results of this study cannot be generalized to the overall
population of postmenopausal women, this study does provide information
that is relevant to the nurse practitioner managing the health of
postmenopausal women. Similar to the results of HERS, this study does not
provide evidence supporting the initiation of estrogen therapy in
postmenopausal women who have a history of a CAD event. The benefit of
initiation of estrogen therapy prior to a CAD event cannot be inferred from
this study. However, the benefits of risk factor modification such as weight
loss and smoking cessation for the promotion of cardiovascular health can be
inferred from the results of this study.
The findings of this study can be related to the nurse practitioner
functioning within Orem’s Self-care Deficit Theory. Based on Orem’s
59
theory, menopause was identified as an existing condition that has a possible
deviation of the development of CAD. Estrogen therapy was identified as a
possible health care deviation requisite of the postmenopausal woman
Although the findings of this study were unable to support the hypothesis of
estrogen therapy as a health deviation requisite, other requisites for the
prevention of CAD were identified. These would include weight control,
smoking cessation, and adequate control of hypertension and diabetes
mellitus. Nursing agency, as related to this study would involve the nurse
practitioner’s ability to identify and appropriately manage the requisites of
risk factor modification.
Recommendations for Future Research
Recommendations for future research were derived from the initial
limitations of this study and from the results of this study.
1. Replicate this study with a larger sample size to include estrogen
users of greater than and less than 6 months duration, and past users who
discontinued therapy in less than 3 years ago.
2. Replicate this study at different facilities and at different locations.
3. Replicate the study and include other risk factors such as
hyperlipidemia, homocystinemia, and positive family history.
60
4. Perform a similar study with the addition of calculating the weight
of each risk factor in the development of CAD in both users and nonusers of
estrogen.
5. Perform a follow-up study of estrogen nonusers with and without
CAD on catheterization for future recurrent CAD events following the
initiation of estrogen therapy prior to hospital discharge.
Summary
This chapter provided a discussion of study results. The hypothesis of
the study was rejected and circumstances influencing this finding were
identified. It cannot be inferred from the results of this study that estrogen
use leads to a decrease in CAD. The results of this study were compared to
results of larger studies published in the literature regarding estrogen use and
CAD. Providing instruction and assisting with risk factor reduction was
identified as a task of the nurse practitioner functioning within a supportive-
educative nursing system as part of Orem’s Theory of Self-care.
The conclusions of this study were discussed and recommendations for
future research were mentioned.
61
References
American Heart Association (1999). Heart and stroke facts: 1999
statistical supplement, Granville, TX: Author.
Barrett-Connor, E., & Bush, T.L. (1991). Estrogen and coronary heart
disease in women. JAMA ,265.1861-1867.
Bush, T.L., Barrett-Connor, E., Cowan, L.D., Criqui, M.H., Wallace,
R.B., Suchindran, C.M., Tyroler, H.A., & Rifkind, B.M. (1987).
Cardiovascular mortality and noncontraceptive use of estrogen in women:
Results from the lipid research clinics program follow-up study. Circulation,
75,1102-1109.
Barry, W.H. (1996). Cardiac catheterization and angiography. In J.C.
Bennett & F. Plum (Eds.), Cecil textbook of medicine (24th ed.) (pp. 208211). Philadelphia: W.B. Saunders Company.
Friedewald, W.T. (1996). Epidemiology of cardiovascular diseases. In
J.C. Bennett., & F. Plum (Eds.), Cecil textbook of medicine (24th ed.) (pp.
170-173). Philadelphia: W.B. Saunders Company.
Greendale, G.A., & Judd, H.L. (1995). Hormone therapy in the
menopause. In P.L. Carr, K.M. Freund, & S. Somani, (Eds.), The medical
care of women (pp. 635-642). Philadelphia: W.B. Saunders Company.
62
Grodstein, F., Stampfer, M.J., Manson, J.E., Colditz, G.A., Willett,
W.C., Rosner, B., Speizer, F.E., & Hennekens, C.H. (1996). Postmenopausal
estrogen and progestin use and the risk of cardiovascular disease. The New
England Journal of Medicine, 335. 453-461.
Guetta, V., & Cannon, R.O. (1996). Cardiovascular effects of estrogen
and lipid lowering therapies in postmenopausal women. Circulation^ 93
1928-1937.
Hartweg, D.L. (1991). Dorthea Orem: Self-care deficit theory. In C.
Metzger McQuiston & A.A. Webb. (Series Eds.), Notes on nursing theories:
Vol 4. (pp. 1-59).
Hulley, S., Grady, D., Bush, T., Furberg, C., Herrington, D., Riggs,
B., & Vittinghoff, E. (1998). Randomized trial of estrogen plus progestin for
secondary prevention of coronary heart disease in postmenopausal women.
JAMA, 280, 605-613.
Matthews, K.A., Kuller, L.H., Wing, R.R., Meilahn, E.N., & Platinga,
P. (1995). Prior to use of estrogen replacement therapy, are users healthier
than nonusers? American Journal of Epidemiology, 143, 971-978.
Matthews, K.A., Meilhan, E., Kuller, L.H., Kelsey, S.F., Caggiula,
A.W., & Wing, R.R. (1989). Menopause and risk factors for coronary heart
disease. The New England Journal of Medicine, 321,641-646.
63
Mosca. L. Manson. IE.. Sutherland, S.E., Langer, R.D., Manolio, T,
& Barrett-Connor, E. (1997). Cardiovascular disease in women: A statement
for healthcare professionals from the American Heart Association.
Circulation, 96, 2468-2482.
Munro, B.H. & Page, E.B. (1993). Statistical methods for health care
research. Philadelphia: J.B. Lippincott Company.
Murabito, J. (1995). Cholesterol screening and management. In P.L.
Carr, K. M. Freund, & S. Somam (Eds.), The medical care of women (pp.
531-541). Philadelphia: W.B. Saunders Company.
Orem, D.E. (1995). Nursing: concepts of practice (5th ed.). St. Louis:
Mosby-Year Book, Inc.
Nabulsi, M.B., Folsom, A.R., White, A., Patsch, W„ Heiss, G., Wu,
K.K., & Szklo, M. (1993). Association of hormone-replacement therapy
with various cardiovascular risk factors in postmenopausal women. The
New England Journal of Medicine, 328,1069-1075.
Ross, R. (1996). Atherosclerosis. In J.C. Bennett & F. Plum (Eds.),
Cecil textbook of medicine (24th ed.) (pp. 291-295). Philadelphia: W.B.
Saunders Company.
Rossouw, J.E., Finnegan. L.P., Harlan, W.R., Pmn, V.W., Clifford, C„
McGowan, J.A. (1995). The evolution of the Women s Health Initiativ
64
perspectives from the NIFL Journal of the Americaan Medical Women’s
Association 50(2), 50-55.
Sacks, F.M. (1995). Is there anything to add to our lipid risk factors
for coronary heart disease? The American Journal of Cardiology, 75,1263-
1264.
Wenger, N.K. (1995). Coronary artery disease. In P.L. Carr, K.M.
Freund, & S. Somani (Eds.), The medical care of women (pp. 543-552).
Philadelphia: W.B. Saunders Company.
Wenger, N.K., Speroff, L., & Packard, B. (1993). Cardiovascular
health and disease in women. The New England Journal of Medicine, 329,
247-253.
Wilson, P.W., Garrison, R.J., Castelli, W.P. (1985). Postmenopausal
estrogen use, cigarette smoking, and cardiovascular morbidity in women
over 50: The Framingham Study. The New England Journal of Medicine,
313,1038-1043.
Witzum, J.L, & Steinberg, D. (1996). The hyperlipoproteinemias. In
J.C. Bennett, & F. Plum (Eds.),
Cecil textbook of medicing (24th ed.) (pp.
1086-1095). Philadelphia: W.B. Saunders Company.
65
Writing group for the PEPI trial (1995). Effects of estrogen or
estrogen/progestin regimens on heart disease risk factors in postmenopausal
women. JAMA, 273,199-208.
66
Appendices
67
Appendix A
CAD and the Role of Estrogen Survey
B
Y
N
1. Is patient 50 years or older?
O O
2. Has the patient had a menstrual cycle within the last 12 months?
o o
3. Is the patient taking estrogen therapy (estrogen [premarin] or progestin/estrogen combinations
[prempro, premphase], do not include transdermal estrogen patches)?
o o
4. If yes to question 3, what is the duration of therapy?
O less than 6 months
O 6 months or greater
5. If no to question 3, has the patient taken estrogen therapy at any time since the onset of menopause?
Y
N
Y
N
O O
6. If yes to question 5, when was therapy stopped?
O less than 3 years ago
O 3 years or greater
7. Height in inches
8. Weight in kg
10. Is the patient receiving any antihypertensive medications?
o o
o o
11. Is the patient receiving any oral antihyperglycemic agents, insulin sensitizing agents, or insulin via injectio
or pump? ....................................................................................................................................................
o o
9. Is the patient a smoker at the time of this admission?
12. Does the patient have a history of CAD (history of cardiac cath showing lesions - or >50%,
previous MI, PTCA/Stent, CABG)?
...........................................................................
13. Presence of CAD on cath (lesion = or >50%)?
..............
Page 1
o o
o o
68
Appendix B
Case Study
The following case study was developed to demonstrate your
understanding of the survey that you will be administering to the subjects of
the study. Please read the case study carefully, then based on the information
of the case study complete the attached survey as if you were interviewing
an actual subject. Answer the questions only upon information presented in
the study.
P.R. is a 58 year old female patient scheduled for a left heart
catheterization. Upon her arrival, you inform her of the study’s purpose and
ask for her verbal consent to participate in the study. Upon interviewing her,
you find that she has not had a menstrual cycle in 4 years. She states that she
was taking premphase 1 year ago, but stopped therapy because of breast
tenderness. She is currently using an estraderm patch once a week to manage
signs and symptoms of menopause. She denies any smoking habit. She
states that she takes hydrochlorothiazide for her blood pressure and rezulin
400mg in the morning for her “sugar”. She also states that she had a cardiac
cath about 3 years ago, and she “didn’t think it showed anything”. After
speaking with the patient, you then look at the chart, which gives a height
and weight of 64” and 1551bs, respectively, and a history which reveals that
the patient had a cath 3 years ago, showing diffuse disease with blockages of
30-40%. P.R. is then taken for her procedure. Review of the chart after the
procedure shows that she now has a 90% lesion in her left circumflex artery.
69
Appendix C
Steps to Obtain Informed Consent
Thank you for participating in the process of data collection for this
study. The study that you are participating in is being performed as part of
the thesis requirement for the MSN degree at Edinboro University. In order
to ensure that the subjects are receiving information regarding participation
in the study in a consistent manner, please follow the guidelines provided
below when obtaining informed consent.
1. Determine initial eligibility for study participation (female patient over
age 50 scheduled for LHC).
2. Inform patient of the following information regarding the study:
• She is being asked to participate in a study of coronary heart disease
in postmenopausal women.
• Participation in the study is voluntary and will not affect outcome of
care received in the lab or amount of time spent in lab.
• All results of the study will be reported in a grouped format.
• All participants will remain completely anonymous.
• Participants will be asked questions regarding menopausal status, use
of estrogen therapy, and cardiovascular risk factors.
• The charts of the participants will be reviewed by the researcher or
assistant for information regarding height, weight, medications, and
results of cath.
• Participation in the study does not involve receiving any
experimental treatment or procedure, and the cardiac catheterization
procedure will be the same as nonparticipants.
3. Allow patient to ask questions regarding this information prior to
obtaining consent. If you are unsure of the answer, please locate the
researcher to assist you.
70
Appendix D
Application to Conduct Research
Page 3 of 3
Investigator’s Statement
I certify that all the information contained in this application is a true and accurate synopsis of the
planned research. I agree to abide by the decisions of the IRB, policies of Saint Vincent and regulations
of the FDA, DHHS and other appropriate agencies. I further a^rec to:
• notify the IRB of any adverse effects, either locally or nationally;
• make no changes except to eliminate immediate hazards and notify the IRB of those
changes;
• monitor the research and report as required;
• alert a subject that may be placed at risk or jeopardy; and
• notify the IRB at the conclusion of the study and submit aAvritten report on noteworthy
.
information or data.
-IODate
Principal Investigator’s Signature
Feasibility and Resources
I agree that it is feasible to conduct this research study in the designated area(s)
re
and can be conducted using Saint Vincent
Surgical
:p;
tel Oftcilities
tent Chair’s Signature
Date
Research Office
This research was deemed (at the time of application) to be in concert with Saint Vincent Health System
mission.
Research Coordinator*s Signature
Type of Research
Research study was:
3/12/99
Exempt
Expedited
Full Review
approved as presented (see letter in file)
delayed, changes required (see letter in file)
changes received on:
approval date:
:___
0 denied (see letter in file)
71
Appendix E
Saint Vincent Health
232 West 25 Street
Erie, Pennsylvania 16544
814/452-5000
Center
SAINT
VINCENT
February 16, 2000
Kris Komosa
Saint Vincent Health Center
232 West 25 Street
Cardiac Cath Laboratory
Erie, PA 16544
Dear Kris:
On February 16,1 approved through expedited review the opening of your protocol titled
“Estrogen Replacement Therapy and Coronary Artery Disease in Women.”
Be advised that as the approved clinical investigator, you will be required to present an
updated report in 5 months at the ERB meeting scheduled for July 17, 2000. Any proposed
changes in the research protocol affecting the subject must be brought to the attention of the
ERB prior to initiation. You, as the clinical investigator, are required to notify the ERB of all
local adverse events.
You may begin the study upon receipt of this letter. Please keep a copy of this letter with the
file about the study. Should you require additional support for your study, please call the
Research Office at (814) 452-5701.
Sincerely,
SAINT VINCENT HEALTH CENTER
Dorothy S. Carlson, DEd, RN, CIM
Secretary
Institutional Review Board
c: K. Komosa, RN