Abstract
Purpose
Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure performed in India. There are fundamental differences between males and females in the incidence and responses of the body to various diseases. These differences are noticeable, more so in conditions relating to cardiovascular health, particularly coronary artery disease (CAD). This study aims to assess the gender differences in the early postoperative outcomes following CABG.
Methods
Between April 1999 through February 2018, 13,415 patients underwent isolated CABG in our practice. Propensity score matching was performed to yield 1825 well-matched pairs in each gender. These groups were compared in terms of various early postoperative outcomes.
Results
There were no significant differences between females and males in terms of early postoperative composite outcomes (4.2% vs. 5.2%) (odds ratio (OR) 0.82; 95% confidence interval (CI) 0.60–1.12, p = 0.213) of 30-day mortality, non-fatal myocardial infarction (MI), non-fatal cerebrovascular accidents (CVA), and need for renal replacement therapy (RRT), 30-day mortality (0.7% vs. 0.7%) (OR 1.11; 95%CI 0.50–2.45, p = 0.796), MI (2.7% vs. 3.1%) (OR 0.93; 95%CI 0.63–1.37, p = 0.708), CVA (0.4% vs. 0.8%) (OR 0.46; 95%CI 0.19–1.14, p = 0.096), and need for RRT (0.7% vs. 0.7%) (OR 0.88; 95%CI 0.40–1.93, p = 0.753).
Conclusion
Females have similar early postoperative outcomes compared to males in terms of composite outcomes of 30-day mortality, non-fatal MI, non-fatal CVA, and RRT among patients undergoing CABG. The outcomes are also similar when individually assessed. The off-pump technique has no additional benefit compared to the on-pump technique in females undergoing CABG.
Keywords: Gender differences, Sex, Female, CABG, Coronary artery bypass surgery, CAD, Coronary artery disease
Introduction
Coronary artery bypass grafting (CABG) is the most commonly performed cardiac surgical procedure today. It is estimated that 150,000 patients undergo CABG annually in India [1], of which 15–20% are females. There is an increasing awareness of fundamental differences between males and females in every aspect of medicine, and coronary artery disease (CAD) is no exception. In the Western population, females undergoing CABG surgery are known to have worse early and late outcomes than males. While the published evidence in the Western population regarding gender differences in CABG is aplenty [2], similar data for the Indian population regarding gender differences is scarce. Hence, we set out to evaluate the effect of gender on early postoperative outcomes of CABG surgery from our two-decade experience.
Methods
From April 1999 through February 2018, 13,415 patients underwent isolated CABG by our team. All these patients were considered for the study. Patients who underwent redo CABG, or any concomitant procedures, were excluded from the study population. Data were extracted from the institutional database’s electronic health records and divided into two groups based on gender. The groups were compared with each other in terms of various preoperative characteristics. Propensity score matching (PSM) was performed to reduce selection and treatment allocation bias. A team of five surgeons performed CABG during the entire study period.
Complete revascularization was defined as the number of observed grafts equal to or more than the number of intended grafts. Composite outcomes were considered the primary outcome. Composite outcomes in the current study have been defined as the cumulative incidence of postoperative 30-day mortality, non-fatal myocardial infarction (MI), non-fatal cerebrovascular accident (CVA), and need for renal replacement therapy (RRT). Secondary outcomes included 30-day mortality, non-fatal MI, non-fatal CVA, need for RRT, re-exploration rates, postoperative atrial fibrillation (AF), deep sternal wound infection (DSWI), and postoperative hospital stay. Because of the retrospective nature of this study, the need for individual patient consent was waived.
Definitions
Post-operative MI was defined as electrocardiograhic (ECG) changes consistent with infarction (new significant Q waves in two contiguous leads in the absence of previous left ventricular hypertrophy (LVH), or conduction abnormalities) or evolving ST segment to T wave changes in two contiguous leads, or new left bundle branch block, or ST segment elevation requiring thrombolysis or percutaneous coronary intervention (PCI), and cardiac markers (troponins or creatinine kinase myocardial band (CK-MB)) in the necrosis range. Non-fatal CVA was defined as new acute focal neurological deficit (except for subarachnoid hemorrhage which may not be focal) thought to be of vascular origin with signs or symptoms lasting greater than 24 h.
Usage of ≥ 5 μg of dobutamine or ≥ 0.05 μg of noradrenaline/adrenaline or the usage of ≥ 2 inotropic agents (both at 24 h post-surgery) was considered as a significant inotropic support.
Statistical methods
We grouped the patients who underwent isolated CABG surgery into two separate groups according to their gender. Both groups were significantly different from each other in terms of various preoperative variables. The following preoperative characteristics were included in a logistic regression model to generate propensity scores: age, hypertension (HTN), diabetes mellitus (DM), dyslipidemia, MI, CVA, peripheral vascular disease (PVD), chronic kidney disease (CKD), emergency status, the extent of CAD, and the type of surgery (on-pump or off-pump technique). PSM, performed with SPSS version 28 using the nearest neighbor matching method with an optimal caliper size of 0.05, yielded 1825 well-matched pairs from both sexes. Both groups had fewer differences in terms of various preoperative variables after the matching (Table 1). A few variables that were not balanced after PSM were included in a multivariate logistic regression model to compare the adjusted risk (adjusted odds ratio with 95% confidence interval (CI)) of various postoperative outcomes with the male gender as reference variable (Fig. 1).
Table 1.
Baseline preoperative and intraoperative characteristics of males and females undergoing CABG
| Variable | Males (n = 11,590) |
Females (n = 1825) |
p-value | Males (N = 1825) |
Females (N = 1825) |
p-value | |
|---|---|---|---|---|---|---|---|
| Age (mean ± SD) (years) | 58.63 ± 8.71 | 59.46 ± 8.4 | < 0.001 | 59.48 ± 7.6 | 59.46 ± 8.4 | 0.929 | |
| Hypertension (%) | 4628 (60.1) | 863 (47.3) | < 0.001 | 855 (46.8) | 863 (47.3) | 0.791 | |
| Diabetes mellitus (%) | 5786 (49.9) | 963 (52.8) | 0.024 | 958 (52.5) | 963 (52.8) | 0.868 | |
| Dyslipidemia (%) | 4651 (40.1) | 672 (36.8) | 0.007 | 640 (35.1) | 672 (36.8) | 0.27 | |
| Preoperative MI (%) | < 4 weeks | 900 (7.7) | 128 (7.01) | 0.95 | 149 (8.1) | 128 (7.01) | 0.92 |
| > 4 weeks | 3838 (33.1) | 570 (31.2) | 516 (28.3) | 570 (31.2) | |||
| NYHA classification (%) | 1 | 90 (0.8) | 13 (0.7) | 0.073 | 24 (1.3) | 13 (0.7) | 0.20 |
| 2 | 8519 (73.5) | 1331 (72.9) | 1298 (71.1) | 1331 (72.9) | |||
| 3 | 1853 (16) | 328 (18) | 1331 (18.2) | 328 (18) | |||
| 4 | 1128 (9.7) | 153 (8.4) | 170 (9.3) | 153 (8.4) | |||
| LMCA disease (%) | 1275 (11) | 218 (11.9) | 0.23 | 205 (11.2) | 218 (11.9) | 0.5 | |
| Preoperative PVD (%) | 1182 (10.2) | 150(8.2) | 0.009 | 96 (5.3) | 150 (8.2) | < 0.001 | |
| Preoperative CVA (%) | 458(4) | 67(3.7) | 0.566 | 32 (1.8) | 67 (3.7) | < 0.001 | |
| Preoperative CKD (%) | 2423 (20.9) | 336 (18.4) | 0.014 | 268 (14.7) | 336 (18.4) | 0.002 | |
|
Type of procedure (%) |
Emergency | 1150 (1.3) | 45(2.5) | < 0.001 | 28 (1.5) | 43 (2.2) | 0.072 |
| Elective | 11,440(98.7) | 1780 (97.5) | 1797 (98.5) | 1782 (97.8) | |||
|
Extent of CAD (%) |
SVD | 256(2.2) | 57(3.1) | 0.002 | 26 (1.4) | 57 (3.1) | < 0.001 |
| DVD | 1581 (13.6) | 288 (15.8) | 218 (11.9) | 288 (15.8) | |||
| TVD | 9753 (84.2) | 1480 (81.1) | 1581 (86.6) | 1480 (81.1) | |||
|
Ejection fraction (%) |
Poor (< 35%) |
754 (6.5) | 99 (5.4) | 0.213 | 97 (5.3) | 99 (5.4) | 0.415 |
|
Fair (35–45%) |
8682 (74.9) |
1383 (75.8) |
1415 (77.5) | 1383 (75.8) | |||
| Good (> 45%) |
2154 (18.6) |
343 (18.8) | 313 (17.2) | 343 (18.8) | |||
|
Type of surgery (%) |
On-pump | 5152 (44.5) | 784(43) | 0.23 | 753 (41.3) | 784 (43) | 0.299 |
| Off-pump | 6438 (55.5) | 1041 (57) | 1072 (58.7) | 1041 (57) | |||
| No. of grafts (%) | ≤ 3 | 6342 (54.7) | 1144 (62.7) | < 0.001 | 978 (53.6) | 1144 (62.7) | < 0.001 |
| > 3 | 5248 (52.3) | 681 (37.3) | 847 (46.4) | 681 (37.3) | |||
| Complete revascularization (%) | 11,086 (95.7) | 1723 (94.4) | 0.018 | 1735 (95.1) | 1723 (94.4) | 0.374 | |
| Single arterial grafting (LIMA usage) (%) | 11,135 (96.1) | 1739 (95.3) | 0.11 | 1758 (96.3) | 1739 (95.3) | 0.12 | |
MI, myocardial infarction; PVD, peripheral vascular disease; CVA, cerebrovascular disease; CKD, chronic kidney disease; CAD, coronary artery disease; SVD, single-vessel disease; DVD, double-vessel disease; TVD, triple-vessel disease
Fig. 1.
The effect of female gender on various early postoperative outcomes of CABG
Descriptive statistics have been used to describe continuous data as numbers, mean ± deviation; and categorical data as frequencies and percentages. The normality of continuous data was assessed using the Shapiro–Wilk test. Continuous data were compared using the t-test and Mann–Whitney test, where appropriate. The categorical preoperative characteristics were compared between both groups using the Chi-square test. All tests were two-sided. A value of p less than 0.05 was considered as statistically significant. IBM SPSS version 28 was used for performing the statistical analyses. MedCalc version 20.0 was used to generate Forest plots.
Results
Table 1 describes the baseline preoperative and intraoperative characteristics of both cohorts (genders) before and after PSM. The female patients undergoing CABG were significantly older than the male patients before PSM. There was a higher prevalence of HTN (p < 0.001), dyslipidemia (p = 0.007), preoperative MI (p = 0.028), preoperative CKD (p = 0.014), preoperative PVD (p = 0.009), and triple vessel disease (TVD) (p = 0.002) in males, whereas DM (p = 0.024) and emergent status (p < 0.001) were significantly higher in the females. However, fewer differences were found between both groups after PSM in most variables except for PVD (p < 0.001), CVA (p < 0.001), CKD (p = 0.002), and extent of CAD (p < 0.001).
There was significant difference in terms of graft usage, with females being more likely to receive ≤ 3 grafts compared to males (62.7% vs. 53.6%, p < 0.001); but, there was no difference between females and males in terms of achieving complete revascularization (94.4% vs. 95.1%, p = 0.374).
Table 2 compares primary and secondary early postoperative outcomes between males and females that were adjusted for differences in preoperative variables including PVD, CKD, CVA, and extent of CAD. There were no significant differences between females and males in terms of composite outcomes (4.2% vs. 5.2%) (odds ratio (OR) 0.82; 95% confidence interval (CI) 0.60–1.12, p = 0.213), 30-day mortality (0.7% vs. 0.7%) (OR 1.11; 95%CI 0.50–2.45, p = 0.796), MI (2.7% vs. 3.1%) (OR 0.93; 95%CI 0.63–1.37, p = 0.708), need for RRT (0.7% vs. 0.7%) (OR 0.88; 95%CI 0.40–1.93, p = 0.753), and CVA (0.4% vs. 0.8%) (OR 0.46; 95%CI 0.19–1.14, p = 0.096). Female and males had re-admission rates of 3.5% and 2.8%, respectively (p = 0.18). The major causes for readmission were leg wound infection, pulmonary complications (lung atelectasis, pleural effusion), congestive cardiac failure, fever, and post-operative angina. There was no significant difference in terms of re-exploration rates (p = 0.56), postoperative AF (p = 0.84), DSWI (p = 0.77), and postoperative hospital stay (p = 0.067).
Table 2.
Comparison of primary and secondary early (30-day) postoperative outcomes between the male and the female groups undergoing CABG
| Variable | Males (N = 1825) |
Females (N = 1825) |
Odds ratio (with 95%CI) (male as reference) | p-value |
|---|---|---|---|---|
| Composite outcomes (%) | 94 (5.2) | 77 (4.2) | 0.82; 0.60–1.12 | 0.213 |
| 30-day mortality (%) | 12 (0.7) | 13 (0.7) | 1.11; 0.50–2.45 | 0.796 |
| Post-operative MI (%) | 56 (3.1) | 50 (2.7) | 0.93; 0.63–1.37 | 0.708 |
| Post-operative CVA (%) | 15 (0.8) | 7 (0.4) | 0.46; 0.19–1.14 | 0.096 |
| Post-operative AKI requiring RRT (%) | 13 (0.7) | 13 (0.7) | 0.88; 0.40–1.93 | 0.753 |
| Re-exploration rate (%) | 61 (3.3) | 59 (3.2) | 0.89; 0.62–1.29 | 0.561 |
| Post-operative AF (%) | 111 (6.1) | 109 (6) | 0.97; 0.73–1.27 | 0.836 |
| Deep sternal wound infection (%) | 22 (1.2) | 24 (1.3) | 1.09; 0.60–1.95 | 0.771 |
| Need for IABP support (%) | 31 (1.7) | 43 (2.4) | 1.40; 0.87–2.24 | 0.156 |
| Significant inotropic support (%) | 682 (37.4) | 711 (39) | 1.00; 0.87–1.15 | 0.986 |
| Pulmonary complication (%) | 55 (3) | 51 (2.8) | 0.95; 0.62–1.36 | 0.693 |
| Post-operative hospital stay (days) median (25th to 75th interquartile range) | 7 (6–8) | 7 (6–8) | 1.00 | 0.067 |
MI, myocardial infarction; CVA, cerebrovascular disease; AKI, acute kidney injury; RRT, renal replacement therapy; AF, atrial fibrillation; IABP, intra-aortic balloon pump
Table 3 presents the comparison of composite outcomes between males and females in different sub-groups.
Table 3.
Comparison of composite outcomes between males and females in different sub-groups
| Sub-groups | Composite Outcomes | p-value | ||
|---|---|---|---|---|
| Males | Females | |||
| Age | > 65 (%) | 32 (6.4) | 27 (4.9) | 0.30 |
| < 65 (%) | 62 (4.7) | 50 (3.9) | 0.33 | |
| Technique (%) | On-pump | 42 (5.6) | 35 (4.5) | 0.31 |
| Off-pump | 52 (4.9) | 42 (4) | 0.36 | |
| Chronic kidney disease (%) | Yes | 8 (3) | 13 (3.9) | 0.55 |
| No | 86 (5.5) | 64 (4.3) | 0.11 | |
| Hypertension (%) | Yes | 64 (7.5) | 49 (5.7) | 0.13 |
| No | 30 (3.1) | 28 (2.9) | 0.81 | |
| Diabetes mellitus (%) | Yes | 66 (6.9) | 45 (4.7) | 0.03 |
| No | 28 (3.2) | 32 (3.7) | 0.58 | |
| Preoperative myocardial infarction (%) | Yes | 43 (6.5) | 25 (3.6) | 0.01 |
| No | 51 (4.4) | 52 (4.6) | 0.80 | |
| Preoperative cerebrovascular accident (%) | Yes | 4 (12.5) | 3 (4.5) | 0.30 |
| No | 90 (5) | 74(4.2) | 0.25 | |
| Emergency status (%) | Emergent | 2 (7.1) | 4 (8.9) | 1.00 |
| Elective | 92 (5.1) | 73 (4.1) | 0.14 | |
Discussion
This propensity-matched analysis of 3650 patients comparing males and females who underwent CABG demonstrates a similar risk of composite outcomes of postoperative 30-day mortality, non-fatal MI, non-fatal CVA, and requirement for RRT. Secondary outcomes of 30-day mortality, non-fatal MI, non-fatal CVA, and requirement for RRT were also similar between both genders (Fig. 1). However, numerous studies [3–6] have consistently shown that females undergoing CABG have worse postoperative short-term outcomes than males. The etiology of these gender differences in outcomes may be due to the basic anatomical, physiological, genetic, and socio-cultural factors, including uneven body frames, uneven risk profiles, referral biases, and guideline-discordant practices for revascularization among women [2]. Although the unadjusted rates of postoperative outcomes were in complete agreement across various studies, showing females having 2–3% higher rates [6, 7] of mortality, the adjusted rates of various postoperative outcomes have been inconclusive, with some studies showing female gender as an independent predictor of mortality [7, 8] while a few others did not [3, 9, 10].
The effect of gender on the risk of postoperative outcomes after CABG may be governed by a complex interplay of factors, out of which racial disparities may also have a role. Most studies [7, 8] that concluded with female gender as an independent risk factor for adjusted-mortality rates were from the Western literature, which could not be verified by other studies [5, 9, 10], especially so, in the Asian population [11] and a subset of the Asian population [12]. The SYNTAX trial [13], in the Western population, showed a significant gender interaction for revascularization strategy favoring females undergoing CABG over percutaneous coronary intervention (PCI) due to better mortality outcomes in females using CABG. However, this was not seen in a follow-up analysis [14]. Hence, the female gender was later eliminated as a factor for estimating risk in the SYNTAX II score [14]. Additionally, the PRECOMBAT trial [11] in the Asian population and a meta-analysis [11] of multiple trials (SYNTAX, PRECOMABT, BEST) also showed that both genders have similar outcomes. Therefore, they also suggested that gender should not be a part of the risk scores for Asian patients undergoing revascularization or a need for recalibration of the SYNTAX score for the Asian population. A similar observation by Zindrou et al. [15] noted that the female gender was predictive of mortality in the Caucasian population (OR 3.803, 95%CI 1.864–7.758) but not so much in the Asian subpopulation (OR 1.190, 95%CI 0.421–3.36) primarily due to a relatively increased mortality rate in Asian men.
The present study showed a similar rate of early postoperative MI after CABG in both sexes. Most studies [7, 9] demonstrated worse rates of early postoperative MI in females after CABG, whereas a few other studies demonstrated similar or even lower rates [3, 16]. In contrast to most studies [4, 7, 17] and even meta-analysis [18] that have stated female gender as a risk factor for early postoperative stroke after CABG, the present study has shown no gender-specific differences in the rate of early postoperative CVA consistent with other studies [2, 10].
In contrast to the study by Puskas et al. [19] that demonstrated better early postoperative outcomes in females with off-pump coronary artery bypass (OPCAB) compared to on-pump CABG, this study did not show better early postoperative outcomes in females with OPCAB. The present study showed that females were more likely to receive ≤ 3 grafts compared to males who received ≥ 4 grafts, which is consistent with other studies [2, 20], citing the demanding nature of performing an anastomosis on the smaller and thinner coronary arteries [19] of females as the possible reason. Aricatt et al. [21] showed a significantly smaller size of the coronary artery in females of the Indian population at various segments of the left main coronary artery, the left anterior descending artery, the left circumflex artery, and the right coronary artery. The lower number of graft usage in females may also be due to the lower prevalence of TVD in females in this study, also observed in another study [20]. An analysis of 1.2 million patients from the Society of Thoracic Surgeons database by Jawitz et al. [2] also revealed a significantly decreased usage of multi-arterial grafting and complete revascularization in females due to various reasons. The lower number of graft usage in females has been proposed to cause the higher adverse early postoperative outcomes observed in females. However, despite the lower number of graft usage in females, the current study showed that achieving complete revascularization can ensure similar early postoperative outcomes in females undergoing CABG compared to males. Likewise, studies have shown no association between the number of graft usage and early postoperative outcomes, as long as complete revascularization is achieved [20].
Limitations
This is a single-center study; so, generalization of the results of this study should proceed with caution. It is ideal to use the inverse probability of treatment weighting (IPTW) to increase the sample size. Due to logistic issues, we used version 28 with a caliper width of 0.05.
The PSM in this study did not result in an equitable distribution of all of the participating variables as there was significant difference between the distribution of PVD, CVA, CKD, and extent of CAD between both genders even after the matching. Although PSM reduces selection and treatment allocation bias, it cannot completely eliminate them due to the variables that were not accounted for in the PSM analysis. In addition, the retrospective nature of this study also introduces some bias. Finally, the lack of standardized definitions for diagnosing various outcomes could make the differences less distinct. The changing definition of MI over time during this long study remains a significant limitation regarding the standardization of reporting of outcomes. Hence, the results of this study should be interpreted in the light of these limitations.
Conclusion
Females have similar early postoperative outcomes compared to males in terms of composite outcomes of 30-day mortality, non-fatal MI, non-fatal CVA, and RRT among patients undergoing CABG. The outcomes are also similar when individually assessed.
Acknowledgements
We thank Nayini Srikanth Reddy, BTech (ECE), Star Hospitals, Hyderabad, India, for assisting in data retrieval and compilation.
Funding
None.
Data Availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Declarations
Ethics approval
This study was approved by the institutional ethics committee dated 17.Aug.2022 with the reference no: SH/RS/IEC/2021–2022/1004.
Informed consent statement
Need for informed consent from the patient was waived off due to the retrospective nature of this report.
Conflict of interest
The author(s) declares that there is no conflict of interest.
Statement of human and animal rights
The study complies with the principles of The Declaration of Helsinki, 1964 and its later modifications. No animals were involved and there was no experimental research on human beings.
Footnotes
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.