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Eur J Cardiothorac Surg 2004;26:521-527
© 2004 Elsevier Science NL
Department of Cardiothoracic Surgery, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden
Received 15 February 2004; received in revised form 20 April 2004; accepted 30 April 2004.
* Corresponding author. Tel.: +46-31-342-1000; fax: +46-31-417-991
e-mail: helena.rexius{at}hjl.gu.se
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Abstract |
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 Top Abstract 1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Key Words: Coronary artery bypass grafting • Waiting time • Gender • Mortality
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1. Introduction |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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There is limited knowledge about which factors that influences mortality on the waiting list. Only two studies have been large enough to perform multivariate risk factor analyses for mortality on the waiting list [6,7]. Morgan et al. [6] investigated risk factors in a large Canadian population with moderate waiting times (median 18 days in isolated CABG and 29 days in CABG and valve patients) and we have recently reported data from Swedish CABG patients with a longer median waiting time (55 days) [7]. In both these studies, male gender was one of several independent predictors for mortality while waiting.
There are gender differences in presentation, treatment and outcome in patients with coronary artery disease (CAD) [10–19]. The clinical manifestations of CAD have a later onset in women [10] and at presentation women have more concomitant cardiovascular risk factors [10,11]. Women have more often unstable angina pectoris despite less extensive CAD [11] and an increased mortality after myocardial infarction has also been reported in women [12]. Early studies also reported that women were less likely to undergo CAD evaluation [13,14] and coronary artery bypass grafting (CABG) [15]. Mortality and morbidity after CABG have been reported to be higher in women compared to men [16–19] although it is controversial whether this is an effect of gender per se or a result of more risk factors among women.
In the present study, we investigated the importance of gender for waiting list mortality by comparing baseline data and mortality rate for men and women on the waiting list for CABG. In addition, gender-specific mortality risk before and after surgery was calculated and risk profiles for mortality among CABG patients, from acceptance to the postoperative period, were constructed for men and women.
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2. Materials and methods |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Preoperative data were registered prospectively in a database (CorBase, Journalia AB, Kungälv, Sweden). Deaths from all causes were reported. The causes of death for patients who died on the waiting list were collected from the Cause of Death Register kept by the National Board of Health and Welfare in Sweden (Socialstyrelsen).
2.2. Definitions
Waiting time was defined as the time from acceptance to operation or death. At the end of the study period, 334 patients were still on the waiting list. For these patients, waiting time was defined as the time from acceptance to the end of the inclusion period (June 30, 1999). Operative death was defined as death of all causes within 30 days after surgery. Significant stenosis was defined as a 50% reduction in the vessel diameter measured by angiography. Unstable angina pectoris was defined as a patient who required hospitalisation due to angina symptoms at the time of acceptance. The left ventricular ejection fraction (LVEF) was measured with transthoracic echocardiography in the majority of the cases and, for the remaining patients, with a left ventricular injection during coronary angiography. The severity of symptoms of cardiac failure was classified according to the New York Heart Association (NYHA) [20] and the severity of angina symptoms was classified using the Canadian Cardiovascular Society (CCS) score [21]. The Cleveland Clinic Risk Score was used for perioperative mortality and morbidity risk stratification [22]. Aspirin and clopidogrel were discontinued seven days before surgery except in patients with acute coronary syndromes. The study was approved by the Research Ethics Committee of the Medical Faculty, University of Gothenburg.
2.3. Triage
All the patients were accepted and given priority at a triage with the treating cardiologist, a senior cardiothoracic surgeon and an interventional cardiologist. The decisions were mainly based on the severity of symptoms, extension of coronary disease and left ventricular function. The final decision of acceptance and priority (imperative, urgent or routine) was left to discretion of the senior cardiothoracic surgeon. The patients were prioritised into three groups: (A) Imperative (n=2301, 39%): surgery planned within two weeks, (B) Urgent (n=2127, 36%): surgery planned within 12 weeks and (C) Routine: (n=1436, 25%): the remaining patients. If patient priority was changed during the study period, the final priority was used in the analysis (which explains why some patients with a high priority have a long waiting time carried over from their time in a lower priority group).
2.4. Statistical analysis
The data is generally presented as the means and standard deviations. For waiting times, the medians and interquartile ranges are given. A P-value of <0.05 was considered significant. Students T-test (continuous data) or chi-square test (categorical data) was used to compare baseline variables between men and women. The non-parametric Mann-Whitney U-test was used to compare waiting times and continuous data between the men and women that died on the waiting list and those who survived until surgery. The importance of gender for death on the waiting list and after surgery was determined with a multivariate Poisson regression model [23] with death on the waiting list as the dependent factor. In short, the hazard function of death was assumed to be e(ß0+ß1x1+
+ßkxk), where the coefficients are calculated from the data base and x1,...,xk( are the values of the variables. From the ß-coefficient, a risk ratio (RR) can be calculated as RR=eß. The following preoperative variables were originally included: age, gender, Body Mass Index, left main stenosis, LVEF, NYHA-class, CCS-class, unstable angina, concomitant valve disease requiring surgery, priority group, Cleveland Clinic risk score, chronic obstructive pulmonary disease, preoperative stroke, hypertension, diabetes mellitus, atrial fibrillation, serum-creatinine, blood-hemoglobin and time after acceptance. In the final model, based on factors that were significant in a multivariate analysis, were the following parameters included: gender, unstable angina, planned concomitant aortic valve replacement, priority group, LVEF, Cleveland risk score and time after acceptance [7]. To compare the incidence of death on the waiting list between men and women, the optimal test for comparison of two Poisson distributions was used. Poisson regression was also used to construct risk profiles of the absolute risk of death from acceptance to the postoperative period.
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3. Results |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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3.3. Priority
The highest priority (imperative) were given to more women than men (43 vs 38%, P=0.003, Table 1). Consequently, fewer women received routine priority (21 vs 25%, P=0.002).
3.4. Mortality on the waiting list
In all, 77 patients (1.3%), 64 men (1.4%) and 13 women (1.0%) died while on the waiting list (P=0.25). In the imperative group 28 (1.2%) patients died, 14 within the intended waiting time (14 days) and 14 after the intended time. In the urgent group 32 (1.5%) patients died, 15 within the intended waiting time (12 weeks) and 17 after the intended time. 17 patients (1.2%) died in the routine group. Unadjusted mortality incidence (deaths per time unit) on the waiting list did not differ between men and women (6.2 vs 4.5 deaths/100 patient years, P>0.30). In a multivariate hazard analysis, female gender was associated with a significantly lower risk of death on the waiting list than men (risk ratio 0.42, 95% confidence interval 0.19–0.93, P=0.032).
3.5. Causes of death
Death certificates were available for 75 of the 77 patients (98%) who died while waiting for surgery. For 73 of the patients (97%), death was related to cardiovascular disease (52 acute myocardial infarction, 11 sudden death, 7 heart failure, 2 stroke, 1 ruptured aortic aneurysm). For two of the patients (3%), the cause of death could not be explained by cardiovascular disease (one gastrointestinal bleed and one trauma). There were no differences in cause of death between men and women.
3.6. Gender specific baseline variables in survivors vs non-survivors
Women that deceased on the waiting list were significantly older (75±6 vs 68±9 years, P<0.001) and had more often unstable angina pectoris (54 vs 25%, P=0.015) compared with women who survived until surgery, Table 2.
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3.7. Operative mortality
The overall 30-day mortality (2.2%) was significantly higher for women than for men (3.9% vs 1.7%, P<0.001). The adjusted mortality risk after surgery did not differ between men and women (RR 0.99, 95% CI 0.75–1.30, P=0.94).
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4. Discussion |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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Coronary artery disease (CAD) has different patterns in men and women [10]. In the present study, previous reports about gender differences in CAD patients were confirmed since we found marked variation in baseline data between men and women accepted for CABG (Table 1). For instance, women were older, had a higher incidence of planned concomitant aortic surgery, higher operative risk, more co-morbidity, higher NYHA and CCS classification and a higher percentage of unstable angina pectoris compared to men. Further, women had better left ventricular function and less extensive CAD. The majority of these factors have previously been suggested to have an impact on the risk for death while waiting for surgery [6–9]. Age, planned concomitant aortic surgery, high operative risk and unstable angina increase the hazard while better left ventricular function and less extensive CAD may reduce the risk [6–9]. In the present investigation did not unadjusted mortality rate on the waiting list differ between men and women (1.4 vs 1.0%) but after correction for variations in baseline data was female gender associated with a significantly lower risk for death than men (risk ratio 0.42).
It is intriguing that women had a lower mortality risk despite higher incidence of a number of risk factors (age, unstable angina, higher operative risk, etc.). On the other hand, women had a somewhat better left ventricular function compared to men which may reduce the risk, although the difference is small, (60 vs 57%). A comparison of the mean LVEF between men and women may underestimate the importance. When instead the percentage of men and women with severely impaired left ventricular function was calculated, we found that substantially more men had EF<40% (7 vs 9.7%, relative difference 38%, P=0.003). Thus, the little absolute difference in mean LVEF between the genders may conceal an important explanation for the difference in mortality risk between men and women on the waiting list.
Despite almost 6000 patients in the study, does not the size of our material permit a separate multivariate risk factor analysis in men and women, since only 13 of the 1303 women accepted for CABG died while waiting. However, when we compared baseline characteristics for the patients that died while waiting with those who survived to the operation separately for men and women (Table 2), we found interesting differences. Although the numbers are small the results indicate that age and unstable angina may be more important in women and concomitant valve disease, diabetes and ventricular function may be more important in men. This suggests subsequently that different factors may be taken into consideration at triage for men and women but again, the number of deaths is small and the data should be interpreted with caution.
The results of the present study may further suggest that if every other risk factor is similar, women, rather than men, should wait for operation. However, it is premature to interpret the data accordingly. It can not be completely excluded that the variation in mortality risk between men and women is an artefact caused by missing factors in the statistical analyses. Therefore, the results should not be used to allocate priority to patients on the waiting list but the findings have generated an important question and further prospective studies on gender-related differences in mortality on the waiting list for CABG are warranted.
The differences in risk profiles between men and women from acceptance to the postoperative period are shown in Figs. 1 and 2 . The absolute risk for death in patients with different characteristics was calculated with Poisson regression models based on data from all 5864 patients. In Fig. 1, risk profiles for 70 years old men and women with unstable angina, imperative priority, high operative risk and moderately impaired LVEF (40%) are given for two different waiting periods (14 and 28 days). For patients with these characteristics, mortality risk increased during the waiting period and was substantially reduced by CABG. On the waiting list, men had a 2.5-fold increased risk for death compared to women while the risk for death after surgery was comparable between men and women. It could therefore be argued that men with these characteristics have more to gain from CABG than women, which also has been suggested from the Frisc II and the RITA 3 trial in patients with acute coronary syndrome [24,25]. However, also in women there was a substantial reduction in mortality risk after surgery (approximately 45%) and therefore CABG obviously reduces mortality risk in both men and women in this subgroup of patients. A completely different risk profile is given in Fig. 2. In this figure, absolute mortality risk is given for 70 years old men and women with stable angina, low operative risk, routine priority and normal LVEF. The absolute risk for death at any time-point is, as expected, in this patient group much lower compared to the patients in Fig. 1 but also in this group of patients have women on the waiting list a lower risk than men. The risk for death increases during the waiting period for both genders. However, when CABG is performed the risk for death increases further both in women and in men with a short waiting period and do not return to the level before surgery during the immediate postoperative period.
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In summary, the present investigation demonstrates a gender-specific difference in mortality risk on the waiting list for CABG with a substantially lower risk for women. The difference could not be explained by differences in the investigated baseline variables. In addition, it is demonstrated that Poisson regression models, when applied on a sufficiently large patient population, can provide useful data about risk profiles in CABG patients.
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Acknowledgments |
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References |
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TopAbstract1. Introduction2. Materials and methods3. Results4. DiscussionReferences |
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This article has been cited by other articles:
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  H. Rexius, G. Brandrup-Wognsen, A. Oden, and A. Jeppsson Waiting Time and Mortality After Elective Coronary Artery Bypass Grafting Ann. Thorac. Surg., February 1, 2005; 79(2): 538 - 543. [Abstract] [Full Text] [PDF]
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