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 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). 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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