Asian Cardiovasc Thorac Ann 2003;11:293-298
© 2003 Asia Publishing EXchange Ltd
Why Are the Results of Coronary Artery Bypass Grafting in Women Worse?
Bartlomiej Perek, MD,
Marek Jemielity, MD,
Wojciech Dyszkiewicz, MD
Department of Cardiac Surgery, Institute of Cardiology, K Marcinkowski University of Medical Sciences, Poznan, Poland
For reprint information contact: Bartlomiej Perek, MD Tel: 48 61 854 9085 Fax: 48 61 854 9085 email: bperek{at}yahoo.com Department of Cardiac Surgery, Institute of Cardiology, ul. Dluga 1/2, 61-848 Poznan, Poland.
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ABSTRACT
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A study was conducted to assess the early results of isolated coronary artery bypass grafting in women and to determine the risk factors for early postoperative complications. Between January 1994 and July 2001, 1,730 patients (301 women and 1,429 men) underwent isolated myocardial revascularization. Conventional bypass procedure was performed on 1,554 patients (270 female and 1,284 male) and off-pump procedure on 176 patients (31 female and 145 male). Hospital mortality was significantly higher in women than in men (5.6% versus 2.9%). Low cardiac output syndrome developed in 8.6% of women and 8.5% of men. Postoperative myocardial infarction occurred in 5.3% of women and 4.3% of men (p < 0.05). The rate of infectious complications was significantly higher in women (7.0%) than in men (5.8%). The independent risk factors for early mortality in women were left ventricular ejection fraction below 40%, left main disease, and urgent operation. The need for urgent surgery in women was also found to be a significant independent predictor of low cardiac output syndrome and postoperative myocardial infarction. In conclusion, higher hospital mortality and morbidity in women undergoing coronary surgery are partially related to the severity of coronary atherosclerosis and comorbid conditions.
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INTRODUCTION
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The prevalence of coronary artery disease (CAD) is lower in women under 50 years of age than in men of the same age group, but in the 6th decade of life the rates parallel.1 As in the male population, cardiovascular pathology is a leading cause of death in women.2 The absolute number of deaths related to cardiovascular disease in women exceeded that in men in the USA in 1988. Moreover, statistics estimate that in the USA 1 in every 2 women will die of some cardiovascular event, outnumbering deaths due to all cancers combined.2 Women’s circulatory disorders have attracted much less scientific interest than have oncological diseases, including breast cancer. Women were excluded in some clinical studies and prospective trials devoted to cardiac diseases. Today, more women qualify for coronary artery bypass grafting (CABG), and it is assumed that 20% to 30% of CABG patients are female.3 The early postoperative outcome is poorer in women than in men, with higher hospital mortality as well as morbidity.4,5 It has been suggested that this may be related to later referral for surgery. Women tend to be older at the time of operation and have more advanced atherosclerosis of the coronary arteries.6
The aim of our study was to assess if women undergoing isolated CABG are at higher risk of early mortality and morbidity as well as to determine the risk factors for early complications following surgery.
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PATIENTS AND METHODS
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Between January 1994 and July 2001, 1,730 patients, comprising 301 women (17.4%) and 1,429 men (82.6%) at a mean age of 57.4 ± 8.5 years (range, 29 to 78 years), underwent isolated CABG. The number of patients operated on in each year is shown in Figure 1
. Preoperative patient demographics are outlined in Table 1.
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Figure 1. The number of patients who underwent isolated coronary artery bypass grafting (CABG) between January 1994 and July 2001 (figures in parentheses are the proportions of female patients in the overall CABG population).
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Preoperatively, left-sided cardiac catheterization, comprising ventriculography and selective coronary angiography, was performed. During ventriculography, left ventricular end-diastolic pressure and left ventricular ejection fraction (LVEF) were calculated. On coronary angiography, stenosis of the left main coronary artery exceeding 50% and of other arteries exceeding 70% was considered significant. The results of preoperative catheterization are listed in Table 2.
All operations were performed through a median sternotomy. In 1,554 patients (1,284 male and 270 female), conventional coronary artery bypass (CCAB) was performed on cardiopulmonary bypass (CPB) and moderate total body hypothermia (26°C to 28°C). After total CPB with aortic and single venous cannulation had been instituted, cold (4°C) crystalloid cardioplegic solution (St. Thomas’ Hospital formula) at a dose of 10 mg•kg-1 was administered into the aortic root. Cardioplegia was repeated (at a dose of 5 mg•kg-1) after every distal anastomosis. Since 2000, 176 patients (145 male and 31 female) had undergone off-pump coronary artery bypass (OPCAB) operation. The heart was exposed employing a deep pericardial stitch snared to the posterior pericardial wall. The site of distal anastomosis was immobilized with an Octopus III stabilizer (Medtronic, Inc., Minneapolis, MN, USA). Intracoronary shunts (Medtronic, Inc., Minneapolis, MN, USA) ranging from 1.5 to 2.5 mm in diameter were used routinely. The intraoperative data are presented in Table 3.
The following variables were analyzed for association with hospital mortality and morbidity following CABG in women: age, history of myocardial infarction, previous percutaneous transluminal coronary angioplasty, family history of CAD, arterial hypertension, hyperlipidemia, obesity (body mass index > 30), diabetes mellitus, peripheral vascular disease, chronic obstructive pulmonary disease, previous cerebrovascular accident, renal insufficiency, left main coronary artery disease, triple-vessel disease, LVEF below 40%, emergency or urgent operation, complete revascularization, number of implanted grafts, use of the left internal mammary artery (LIMA), aortic crossclamping, and CPB time.
Hospital (early) mortality and morbidity were defined as events that occurred up to 30 days after surgery. Low cardiac output syndrome (LCOS) was diagnosed when systolic arterial pressure was below 70 mm Hg (9.3 kPa), pulmonary capillary wedge pressure exceeded 20 mm Hg (2.7 kPa), and cardiac index was less than 1.8 L•min-1•m-2 (body surface area), despite administration of increasing doses of inotropic drugs and correction of afterload and preload. Postoperative myocardial infarction (PMI) was defined by electrocardiographic criteria (new Q waves, loss of R waves, or new intraventricular conduction defect) and biochemical parameters (serum creatine kinase MB higher than 100 IU•L-1 and cardiac troponin I above 2.0 µg•L-1). Superficial wound infection was considered as infection confined to the subcutaneous tissue, respiratory insufficiency as a need for postoperative ventilation exceeding 12 hours, and renal failure as serum creatinine concentration elevated to above 200 µmol•L-1.
Continuous variables are expressed as mean ± standard deviation. Univariate comparison was computed using the chi-squared test or Fisher’s exact test for categorical variables and t test for continuous variables. Univariate analysis of potential risk factors for early mortality and morbidity was done using the chi-squared test. A p value of less than 0.1 was the criterion for inclusion in the multivariate model. Multivariate analysis was performed by means of a logistic regression model. Results are expressed as odds ratios with 95% confidence limits. In all tests, two-tailed p values < 0.05 are considered statistically significant. All statistical analyses were performed using Statistica 5.0 for Windows (StatSoft Inc., Tulsa, OK, USA).
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RESULTS
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The data on hospital mortality and morbidity are shown in Table 4. The overall hospital mortality was significantly higher in women than in men (5.6% versus 2.9%). Early mortality was significantly higher in the years 1994–1998 than in 1999–2001, in both female and male patients. All women survived and only 1 man died in the early postoperative period after OPCAB. Thus, hospital mortality in the OPCAB group was markedly lower than in the CCAB group. Lower mortality in 1999–2001 was partially, but not solely, related to the excellent early results of OPCAB. The patients died of LCOS, PMI, mediastinitis with sternal instability, respiratory insufficiency, stroke, and renal failure. Multivariate analysis revealed that the independent risk factors for early deaths in women (Table 5) were LVEF below 40%, left main disease, and urgent operation.
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Table 5. Independent Risk Factors for Hospital Mortality, Low Cardiac Output Syndrome, Postoperative Myocardial Infarction, and Inflammatory Events
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During the early postoperative period, 8 women (2.7%) and 40 men (2.8%) required reoperation. The indications for reoperation were mediastinitis with sternal instability (6 women or 2.0% and 18 men or 1.3%) and excessive postoperative bleeding (2 women or 0.7% and 22 men or 1.5%). There was no significant gender difference in the reoperation rate nor in the indications for reoperation.
LCOS developed in 26 women (8.6%) and 121 men (8.5%) (the difference was not significant), including 3 OPCAB cases (1 female and 2 males). Intraaortic balloon pumping (IABP), the treatment of choice for LCOS, was used in 25 female and 118 male patients. Its efficacy was significantly lower in women than in men (18 women or 72.0% versus 99 men or 83.9% successfully treated). IABP was discontinued in 4 men because of ischemic complications. The only complication of IABP in the women was temporary lower extremity ischemia, which was treated successfully with medications. The logistic regression model showed that the predictors of LCOS in women were impaired LVEF and urgent CABG. In the CCAB group, PMI was noted in 15 women (5.6%) and 59 men (4.6%) (p < 0.05). In the OPCAB group, PMI was diagnosed in 1 woman (3.2%) and 2 men (1.4%). The only independent risk factor for PMI was urgent operation.
The rate of infectious complications was significantly higher in women (21 women or 7.0% versus 83 men or 5.8%). The complications comprised mediastinitis in 5 women (1.7%) and 13 men (0.9%) (p < 0.05) and superficial wound infection in 16 women (5.3%) and 70 men (4.9%) (nonsignificant). In the OPCAB patients, only superficial wound infection was noted, in 2 women (6.5%) and 5 men (3.4%) (p < 0.05). The independent risk factors for inflammatory events in women, evaluated with multivariate analysis, were diabetes mellitus and obesity. Other postoperative organ and surgical complications that are listed in Table 4
did not differ between women and men.
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DISCUSSION
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CAD remains a leading cause of death in developed countries both in men and women.7 The incidence of CAD has risen in women. Nowadays, women undergo CABG more frequently,5,8 although some authors reported that during hospitalization for CAD women had fewer major diagnostic and therapeutic procedures (including surgery) than men.9 In our department, women represented less than 12% of all CABG patients in 1995, while in 2001 they made up 23.2% of the CABG population.
Previous studies demonstrated that the outcome of direct myocardial revascularization in women was poorer than in men,5,10 with perioperative mortality ranging from 2.4% to 7.1%.10,11 For instance, in a multicenter coronary artery surgery study of 25,000 patients, women were noted to have a significantly higher operative and hospital mortality of 4.5%, compared to 1.9% in men.8 In our group, 5.6% of women died intraoperatively or early after surgery. It is thought that women are referred for CABG later than men, at a more advanced stage of coronary artery atherosclerosis.6,8 Among our female patients, more than 30% had significant disease of the left main trunk, which is a higher rate than in both the overall and the male CABG population.8,12 Multivariate analysis showed that left main disease was a significant predictor of hospital death. Female patients, usually older than male patients at the time of operation, have lower circulatory capacity and more associated diseases, which influence early and late results.2,10 In our group, the women were older and had a higher incidence of hypertension, hyperlipidemia, diabetes mellitus, morbid obesity (all considered as predictors of atherosclerosis and CAD), as well as impaired LVEF compared to male CABG patients. Some authors suggested that females are at higher risk for early mortality independent of these risk factors.3,11 The reason could be the smaller diameter of vessels, which is partially related to the lower body surface area of women.10 Female patients were found to have an epicardial arterial lumen diameter 9% smaller than that in men, even after normalization for body surface area.13
The risk of CABG in women is becoming lower as a result of increasing experience, introduction of better myocardial protection techniques, and less invasive methods of myocardial revascularization.5 Toronto Hospital reported a marked decrease in CABG mortality from 2.4% in 1982–1984 to 1.0% in 1991–1993.2 Today, despite worsening preoperative clinical status of patients, operative risk is declining for both men and women undergoing CABG, and the previously noted gender differences in mortality are becoming less apparent or are in fact resolving.5 Our observations confirm improved outcome in women undergoing CABG. However, although operative and hospital mortality in our group has dropped in the last few years, gender differences are still observed. Growing experience of our surgical and anesthetic teams (from around 100 procedures in 1995 to above 300 in 2000) resulted in more appropriate patient selection, better preoperative patient preparation, and improved intraoperative management. Moreover, more common use of LIMA grafts is considered beneficial for CABG outcome.14 In our group, LIMA has been used more extensively since 1999. Additionally, the preliminary results of OPCAB in women were very promising. It is likely that the introduction of this method positively affected the early mortality rate in 1999–2001 in both women and men. Because of the small OPCAB sample and the very low mortality and morbidity rates, multivariate analysis was not performed separately for the OPCAB patients.
In our group, LCOS was the most fatal complication following surgery in women, and the need for urgent operation (for patients with unstable angina or left main disease) was one of the significant predictors of LCOS, which is consistent with other studies.15 IABP is an accepted treatment for postcardiotomy LCOS. Its efficacy is estimated at 50% to 70%, and it is reported to be lower in women, elderly patients, and patients in preoperative New York Heart Association functional class III or IV.16 Our results of IABP use in CABG patients are comparable with those of previous reports.15,16 In our group, more men than women treated with IABP for LCOS recovered and were discharged from hospital in satisfactory clinical condition.
PMI was found to be a leading cause of grave events after CABG in some studies,12,17 accounting for 45% to 70% of deaths. In our group, PMI was the second most frequent cause of early mortality, and only the need for urgent operation was an independent risk factor for PMI. Better myocardial protection techniques, shorter ischemia time (i.e., aortic crossclamping time), and less invasive procedures are postulated to lower the incidence of fatal PMI.5 In our group, fewer OPCAB patients, both male and female, developed PMI.
The results of our study reveal that women had more infectious complications after surgery than men. Multivariate analysis shows that diabetes mellitus and morbid obesity were significant independent predictors. These findings are consistent with earlier reports that obesity adversely affects wound healing18 and that diabetes mellitus led to macro- and microvascular diseases that might contribute to infection and delayed wound healing, especially in type II diabetic patients. In addition, hyperglycemia can affect the cellular response (delayed response of polymorphonuclear neutrophils and fibroblasts) to tissue injury.19 Moreover, 37.5% of women in our group had urgent or emergency operation, which, according to commonly accepted risk scales, may contribute to higher postoperative morbidity, including mediastinitis.20
We conclude that high hospital mortality and morbidity in women undergoing CABG are partially related to the severity of coronary atherosclerosis and comorbid conditions.
Presented in part at the 15th Biennial Congress of the Association of Thoracic and Cardiovascular Surgeons of Asia, Mumbai, India, December 6–9, 2001.
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ABSTRACT
INTRODUCTION
