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1993-2003 Gender Differences in Coronary Artery Revascularization: Has Anything Changed?

Edwards, Michelle L. BSN, RN; Albert, Nancy M. PhD, CCNS, CCRN, CNA; Wang, Chaohui MS; Apperson-Hansen, Carolyn MStat

The Journal of Cardiovascular Nursing: November-December 2005 - Volume 20 - Issue 6 - p 461-467
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Background: Gender differences abound in patients undergoing coronary artery bypass graft (CABG) surgery. Most research was conducted in the early 1990s. It is unknown if gender differences have diminished over time.

Research objectives: To determine whether gender differences exist in the current era of CABG surgery by examining preoperative, intraoperative, and postoperative factors known to affect outcomes.

Subjects and methods: In this descriptive, correlational study of all patients undergoing primary, isolated CABG at a large, urban Midwestern healthcare center, data in 1993 and 2003 were analyzed to determine if gender and time differences existed and if there was a time and gender interaction effect. Trained nurses prospectively collected data during the index hospitalization for the institution's Cardiovascular Information Registry.

Results: 2,200 patients were studied; women accounted for one-fourth of the sample. Age over 65 years; current smoking; presence of hypertension, cerebrovascular accident; and insulin-dependent diabetes; symptomatic heart failure and chest pain were significantly associated with female gender (all P's < .001). Intraoperatively, internal mammary arteries were used less as a graft conduit in women (P < .001); gender differences were most pronounced in patients requiring 2 bypass grafts. Postoperatively, cardiac pump failure and median hospital stay were greater in women (both P's < .001); however, both decreased over time.

Conclusions: Gender differences continue to exist in patients undergoing CABG. Differences do not affect hospital mortality rates but play a role in hospital length of stay and may affect postdischarge recovery. Research targeted at modifiable preoperative factors may improve postoperative recovery.

Michelle L. Edwards, BSN, RN Manager of Registry Operations, Clinical Investigations Unit, Department of Thoracic and Cardiovascular Surgery, Cleveland Clinic Foundation, Cleveland, Ohio.

Nancy M. Albert, PhD, CCNS, CCRN, CNA Director of Nursing Research, Division of Nursing and Clinical Nurse Specialist, Kaufman Center for Heart Failure, Cleveland Clinic Foundation, Cleveland, Ohio.

Chaohui Wang, MS Statistical Programmer, Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio.

Carolyn Apperson-Hansen, MStat Research Associate, Department of Biostatistics and Epidemiology, Cleveland Clinic Foundation, Cleveland, Ohio.

Corresponding author Nancy M. Albert, PhD, RN, CCNS, CCRN, CNA, The Cleveland Clinic Foundation, 9500 Euclid Avenue, M-13, Cleveland, OH 44195 (e-mail: albertn@ccf.org).

Coronary heart disease (CHD) is the leading cause of death for both men and women in the United States and in most industrialized countries.1 In the United States, the death rate for cardiovascular disease has declined in men, but it remains unchanged in women.1 Gender differences in CHD have been widely investigated. Distinct gender differences span the scope of CHD, from presentation to management, and include differences in clinical manifestation, perception of condition, validity of diagnostic tests, treatment decisions, response to treatment, and outcomes.

Since the early 1990s, differences in men and women have been identified with respect to CHD presentation, diagnosis, and treatment.2 This background information should have heightened nurses' awareness to develop targeted treatments that reduce gender disparity and improve clinical outcomes. In this paper, characteristics related to gender bias in diagnostic procedure and therapeutic interventions are explored. Then, outcomes from a large, urban, single-center experience of coronary artery bypass graft (CABG) surgery in 1993 and 2003 will be presented to learn if gender differences still exist. Preoperative background, intraoperative techniques, and postoperative complications will be analyzed between genders. Data for women and men will be compared between the two time points to determine if gender bias has diminished over time. If women's CHD and CABG outcomes continue to be inferior compared to those experienced by men, then strategies to improve quality of life of women with CHD is an important developmental focus.

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CHD Presentation, Diagnosis, and Treatment in Women

The onset of clinical manifestations of CHD is later in women.1 Women tended to experience their first myocardial infarction (MI) 10 to 20 years later than men, and their risk of having a second MI was doubled.2 It was suspected that the increased risk of a second MI may have been due to faster progression of coronary artery disease (CAD) in women.2 When older women experienced their first coronary event, they had more comorbid conditions than their younger male counterparts, including diabetes and hypertension.3 Women presented more frequently with unstable angina and non-ST elevation myocardial infarction (NSTEMI), whereas men had myocardial infarction with ST elevation (STEMI).4

Women may experience different sensations and pain than men during an acute coronary syndrome (ACS) event. In one study, 46% of women first seen with acute MI had no chest pain at all. The presenting symptoms were shortness of breath in 80% and epigastric pain in 20%.5 Other researchers reported that women with ACS most often presented with atypical symptoms such as abnormal pain locations, dyspnea, nausea, vomiting, and fatigue.4 In addition, women were more likely to have coronary spasm or chest pain without coronary artery pathology.6

Because women may not experience typical chest pain at the time of an ACS event, they may not believe that they are in danger. Women tend to minimize their cardiac symptoms and seek professional help later than men after an ACS event.4 Until the last decade, the general public, and even some healthcare providers, perceived CHD predominately as a disease of men.1

The diagnosis of CAD is more complex in women than in men, especially since angina may be uncorrelated with the extent of occlusive disease.7 In an Emergency Department, women's electrocardiogram (ECG) were more likely to show higher rates of ST depression and T-wave inversions, rather than ST elevations.4 In addition, low hematocrit and elevated estrogen levels produced suspicious ST-segment alterations on women's ECGs that were similar to those produced by digitalis.2 Thus, an ECG may not be a reliable diagnostic tool for women. Troponins, B-type natriuretic peptides (BNP), and N-terminal proBNP are biochemical markers commonly used for assessing incidence of ACS.4 BNP measurements differ by gender. However, troponin demonstrated higher sensitivity and specificity across gender.4Thus, troponins are the markers of choice for both men and women.4

Historically, women's complaints were seen as less urgent; consequently, they were evaluated less intensively4 and diagnostic testing was less likely to be performed. Women had less referrals for cardiac catheterization after having an abnormal thallium stress test result, when compared with men.8 In a study by Steingart et al,9 15.4% of women and 27.3% of men were referred for cardiac catheterization, even though women reported symptoms of ischemia with greater functional disability as frequently as men. After MI, women were commonly referred for echocardiography, whereas men were more likely referred for Holter monitoring and treadmill testing.2

Gender issues are also apparent with regard to reliability and validity of routine diagnostic tests for CHD; partially due to the fact that diagnostic test development and research was conducted solely in men. In addition, some cardiac scans may be less accurate in women because they scan through breast tissue.2 Exercise single photon emission computed tomography (SPECT) thallium imaging produced better predictability of left-main and three-vessel CAD in women, suggesting that it may be a more reliable diagnostic test.2 As for validity problems, in a study of treadmill exercise testing, researchers reported a false-positive rate in men and women of 8% and 67%, respectively.10

In women, difficulty in diagnosing CHD resulted in treatment delays that may have contributed to less favorable outcomes. In the late 1980s and early 1990s, many researchers11-15 reported a treatment bias in patients with CAD related to fibrinolytic therapies, percutaneous interventions, and CABG. Women had a higher risk for bleeding with all 3 treatment strategies, increasing procedural risk.6 Women did not receive coronary angioplasty and CABG procedures as often as men and they had less favorable outcomes than men after CABG surgery.2 Women had higher rates of operative mortality, perioperative infarction, early and late graft reocclusion, and incomplete revascularization.15,16 In one study of outcomes based on treatment strategy from 1995 to 2000, risk-adjusted relative risks for women were elevated at 3.49 for CABG surgery and 2.38 for percutaneous intervention early after the procedure, compared to men, with subsequent decreases in relative risk between the genders within the first year after treatment.17 Postoperatively, women had less relief of symptoms, more depressive symptoms, and reported lower activity levels than men.12,15,16,18

These less favorable outcomes were attributed to physical and preexisting differences.19 In past CABG studies, women had smaller hearts with smaller, more friable, and more easily occluded coronary arteries than men. Smaller coronary vessels increased the difficulty of surgical intervention.2 In one study of patients undergoing CABG, mortality was associated with older adults and those that were smaller in size (less body surface area) at the time of surgery. Thus, women were at higher risk.3 In many studies, women had more preexisting comorbid conditions that increased their risk for mortality after CABG (eg, unstable angina, congestive heart failure, chronic lung disease, hypertension, diabetes, and depressive symptoms in the month before surgery).3,17,18 Intraoperatively, women had fewer vessels bypassed and internal thoracic artery (ITAs) were used less often as graft conduits.3 Hospital course (hospital mortality and longer stays) was attributed to age (greater than 75 years) in one study conducted in the United States and Canada.19 When independent predictors of cost were analyzed, female gender was significantly associated with increased costs.19 Thus, comorbid and preexisting conditions as well as intraoperative differences help to explain why women had a more difficult recovery after CABG than men.

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Ten-Year CABG Trends: Have We Made Improvements in the Last Decade?

It is important to learn if gender differences resolved with awareness of bias; newer surgical device and anesthesia techniques; and greater experiences in vasoactive and inotropic medications as well as general postoperative care. To learn if gender bias still exists today and if gender bias can be attributed to biological and physiological differences rather than the surgical experience, data of patients who underwent CABG at the Cleveland Clinic Foundation in 1993 and 2003 were compared. The primary aims of this review were to compare the frequency of preoperative, intraoperative, and postoperative risk factors for women with CABG at 2 points, 1993 and 2003, and to determine if there were differences in selected risk factors between genders.

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Methodology: A Comparison of CABG in Women in 1993 and 2003

Since 1972, The Cleveland Clinic Heart Center has sustained a registry of all patients undergoing any cardiac operative procedure. The Institutional Review Board (IRB) at the Cleveland Clinic approves the registry. Members of the research team, including Registered Nurses, using defined criteria, collect data prospectively during the surgical hospitalization episode. For this review, data from patients who underwent CABG in 1993 and 2003 were compared. Patients who had previous cardiac surgery or concomitant cardiac or noncardiac procedures at the time of CABG were excluded from analysis.

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Data Analysis Plan

Logistic regression analysis was used to assess the relationship between gender at 2 time points while controlling for possible preoperative risk factors (specified in Table 1), intraoperative risk factors (Table 2), and in-hospital postoperative risk factors (Table 3). General linear regression analysis was used to assess the relationship of length of hospital stay with gender at 2 time points.

TABLE 1

TABLE 1

TABLE 2

TABLE 2

TABLE 3

TABLE 3

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Results

In the years 1993 and 2003, 2200 patients underwent primary, isolated CABG surgery; 1396 cases in 1993 and 804 cases in 2004. The percentage of women was unchanged over time (25% and 24%, respectively). From 1993 to 2003, the number of primary isolated CABG procedures decreased 42%, despite the increase in CHD in the United States. This decrease was partially attributed to the increase in percutaneous intervention (PCI) procedures performed over the 10-year period. In addition, the Cleveland Clinic Heart Center's national reputation has been based on surgical innovation. Thus, patients were likely to have combination surgery (CABG plus valve, aorta, and/or left ventricular reconstruction surgeries) rather than an isolated CABG during this 10-year period.

Tables 1, 2, and 3 provide a comparison of results for women and men at each time point studied. For each, columns 1 and 2 report the proportion of women and men, respectively, with specific end points in 1993 and 2003. Column 3 shows the P value from logistic or linear regression analysis on2 main effects (gender and time) and the interaction effects of both gender and time for each end point.

Table 1 lists clinical preoperative data for men and women at each time point studied. More men than women had CABG, however women were older and sicker preoperatively. Although CHD is known to present at an older age in women and the effect of being an older female is significant when compared to men (P < .001), the percentage of older women having CABG significantly declined during the 2 study years, 2003 and 1993 (odds ratio, 0.74; 95% confidence intervals, 0.52-1.06; P < .02). This occurred despite an increase in CABG frequency in older men during the same study years. Except for the occurrence of MI, women were significantly more likely to have cardiovascular comorbidities prior to surgery. The incidence of hypertension (odds ratio for hypertension, 3.0; 95% confidence intervals, 1.83-4.93; P < .0001) and congestive heart failure (odds ratio for congestive heart failure, 3.0; 95% confidence intervals, 1.38-6.35; P < .0054) increased with time. Woman had significantly more cardiac symptoms reflecting a poorer quality of life preoperatively at both time points. Of note, New York Heart Association functional class was less severe in 2003, compared with 1993 for both genders. Thus, patients having surgery in 2003 generally had a greater preoperative cardiac risk profile but fewer symptoms restricting activities of daily living.

Table 2 presents intraoperative data for men and women having CABG. In addition to the emergency procedure data presented below, women were less likely to have a graft using an ITA. This gender finding was also significant over time, reflecting a continued gender bias in graft conduit selection. A striking difference was also noted in the frequency of 2 ITAs used during the CABG procedure. Although the percentage of three (or more)-vessel disease was similar between men and women at both study points, very few women received grafts using 2 ITA conduits, compared to nearly 25% of men.

Table 3 lists clinical postoperative complications, median hospital length of stay (LOS), and hospital mortality for men and women after CABG. Postoperative cardiac (pump) failure was a significant condition in women, as noted by intra-aortic balloon pump frequency. The effect of time was not significant; however, this could be due to the small number of events. Interestingly, the effect of being a woman, the effect of time, and the interaction effect of gender and time did not play a role in non-pump failure postoperative complications. Women had significantly longer hospital LOS as compared to men, and the LOS significantly decreased in 2003 when compared to 1993 (odds ratio, 0.82; 95% confidence intervals, 0.57-1.17); however, the interaction effect of gender and time was nonsignificant. Because complication rates were not significantly different in men and women, analysis of variance was used to determine if variables associated with female gender were also associated with a longer hospital LOS. Table 4 provides results. The total variance accounted for with this model was 11%, suggesting that a longer LOS in women was related to objective or subjective preoperative, intraoperative, and postoperative characteristics that were not collected in this registry (such as regional differences, noncardiovascular related comorbidities, emotions, appetite, pain, locus of control, etc).

TABLE 4

TABLE 4

As expected, hospital mortality declined for both men and women. Although the effect of time and gender were nonsignificant, the relative risk of hospital mortality for women in 2003 as compared with 1993 was 0.22 (95% confidence intervals, 0.03-1.73), representing a combination of improved preoperative health of women, intraoperative technical and device advances, and excellence in postoperative care. For both men and women, advanced age (P = .001) and cardiac symptoms that limited functional ability (NYHA functional class) (P = .005) were strong predictors of hospital mortality (Table 5).

TABLE 5

TABLE 5

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Is There a Difference in End Points in Women Over Time?

Cleveland Clinic trends are similar to older reports in the literature. Others also reported that women were older and had more cardiovascular risk factors at the time of surgery.11,20-22 In patients treated at the Cleveland Clinic, the prevalence of women having 3 or more diseased coronary artery vessels increased from 64% in 1993 to 75% in 2003. However, women were less likely to receive 2 ITA grafts, even though the literature supports the use of 2 ITA grafts as conduits. Early researchers did not discuss why ITA grafts as conduits were used less often in women. A more recent single-center study of left ITA utilization during CABG showed great variability in the use of LITAs as conduits and that women were less likely to receive one.23 Left ITA graft use was associated with lower early morbidity and mortality and a decrease in hospital LOS.23 Two authors (MLE and NMA) questioned two cardiovascular surgeons from Cleveland Clinic for explanations and rationale for our observations and findings in the literature. Both replied that there is bias and surgeon preference when making this surgical decision and may be due to older age of women at the time of revascularization. Since current research consistently demonstrates equal postoperative morbidity and mortality risk when ITA grafts are used, it is important to learn if other differences exist between genders when ITA grafts are used. New research may facilitate less gender bias in conduit type during CABG procedure.

Finally, researchers reported that women had a more difficult recovery compared to men after CABG surgery that was not explained by presurgical health status or other patient characteristics.18 Based on hospital LOS, Cleveland Clinic data supported this finding. Although the postoperative complication rate between men and women was low and similar at both time points, in 2003, women had significantly higher rates of septicemia, ventricular arrhythmia, cardiac failure (represented by intra-aortic balloon pump data), and sternal wound infection than men. These results provide evidence for continued diligence in developing, implementing, and evaluating interventions to decrease modifiable cardiovascular disease risk factors and improve outcomes for women after CABG.

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Nursing Implications

In view of ongoing gender differences in CHD and post-CABG, nurse researchers need to focus on new or tailored assessment and interventions that decrease modifiable cardiovascular risk factors, enhance screening of preoperative risk, and facilitate early postoperative recovery following CABG surgery for both men and women. In our study, chest pain and symptoms associated with higher NYHA functional class were associated with both increased LOS in women and increased hospital mortality in men and women. Further study of predictors of functional outcomes or of preoperative or postoperative interventions that affect functional outcomes might lead to improved hospital and postdischarge outcomes, especially because these factors can be modified with medications and lifestyle changes.

There are many areas of women's patterns of recovery after CABG that have received attention, especially in the last decade. Nursing research has focused on symptoms; activity; emotional health; perceptions of health status, capabilities, and return to health; quality of life; processes women undergo when having cardiac surgery; healing and interventions aimed at improving education and communication (advance practice nurse or home care nurse interventions). However, there is still a need for new nursing research that might improve the hospital course to decrease hospital LOS. Little research is available on noncomplication risk factors for longer LOS; for example, anemia due to normal blood loss while hospitalized, treating a low preoperative albumin level before surgery, or early postoperative pain and functional capabilities when ITA grafts are used. Assessing these phenomena by gender and conducting experimental trials to reduce LOS might promote practice changes.

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Conclusion

The gender- and time-related single-center findings presented in this study illustrate that gender differences still exist in patients undergoing CABG. Preoperative differences between genders accounted for the majority of variation, and were due to a combination of age, comorbid conditions, and symptoms. Although some factors, especially symptoms, were the precursor to using CABG as a treatment strategy, women had higher rates of clinical heart failure, chest pain, and worsened functional status compared to men, all of which are modifiable with medication and lifestyle alteration and optimization. Intraoperatively, women continue to have less graft conduits using ITAs. This could lead to incomplete revascularization and promote worsened functional status and symptoms during postoperative recovery. Postoperatively, women are more likely to have cardiac dysfunction and longer hospital stays, and these trends were not related to time. Nursing research is needed in many areas to improve recovery outcomes.

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REFERENCES

1. Wenger NK. You've come a long way, baby cardiovascular health and disease in women problems and perspectives. Circulation. 2004;109:558-560.
2. Beery TA. Diagnosis and treatment of cardiac disease. Heart & Lung. 1995;24:427-435.
3. Williams MR, Choudhri AF, Morales DLS, et al. Gender differences in patients undergoing coronary artery bypass surgery, from a mandatory statewide database. J Gend Specif Med. 2000;3(1):41-48.
4. Elsaesser A, Hamm CW. Acute coronary syndrome the risk of being female. Circulation. 2004;109:565-567.
5. Rankin SH. Response to women recovering from coronary artery bypass surgery. Scholarsh Inq Nurs Prac. 1993;7:245-248.
6. Hochman JS, Tamis-Holland JE. Acute coronary syndromes. Does sex matter? JAMA. 2002;288:3161-3164.
7. Glazer MD, Hurst JW. Coronary atherosclerotic disease: some important differences in men and women. Am J Noninvasive Cardiol. 1987;1:61-67.
8. Chiriboga DE, Yarzebski J, Goldberg RJ, et al. A community-wide perspective of gender differences and temporal trends in the use of diagnostic and revascularization procedures for acute myocardial infarction. Am J Cardiol. 1993;71:268-273.
9. Steingart RM, Packer M, Hamm P, et al. Sex differences in the management of coronary artery disease. N Engl J Med. 1991;325:226-230.
10. Rimmer LM. Heart disease and older women. J Women Aging. 1993;5:101-117.
11. Ayanian JZ, Epstein AM. Differences in the use of procedures between women and men hospitalized for coronary artery disease. N Engl J Med. 1991;325:221-225.
12. Khan S, Nessim S, Gray R, Czer LS, Chaux A, Matloff J. Increased mortality of women in coronary artery bypass surgery: evidence for referral bias. Ann Intern Med. 1990;112:561-567.
13. Tobin JN, Wassertheil-Smoller S, Wexler JP, et al. Sex bias in considering coronary artery bypass surgery. Ann Intern Med 1987;107:19-25.
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19. Chee JH, Filion KB, Haider S, Pilote L, Eisenberg MJ. Impact of age on hospital course and cost of coronary artery bypass grafting. Am J Cardiol. 2004;93:768-771.
20. Hawthorne MH. Gender differences in recovery after coronary artery surgery. IMAGE J Nurs Scholarsh. 1994;26:75-80.
21. Krumholz HM, Douglas PS, Lauer MS, Pasternak RC. Selection of patients for coronary angiography and coronary revascularization early after myocardial infarction: isthere evidence for a gender bias? Ann Intern Med. 1992;116:785-790.
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23. Dabal RJ, Goss R, Maynard C, Aldea GS. The effect of left internal mammary artery utilization on short-term outcomes after coronary revascularization. Ann Thorac Surg. 2003;76:464-470.

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Keywords:

CABG; coronary artery disease; coronary heart disease; gender differences; women

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