Impact of Sex Difference on Early Postoperative Outcomes in Elderly Patients Undergoing Off-Pump Coronary Artery Bypass Surgery: Are Women Really More Unfortunate Than Men?

Introduction

Female sex is generally considered as a significant predictor of mortality following coronary artery bypass grafting (CABG) surgery. It has been reported that the risk of perioperative mortality following CABG is 1.5 to 2 times in women than men [1–3]. Many studies have been conducted on the reasons and consequences of this significant difference between male and female sexes, and the relevant subject has become the focus of attention in the literature. The clinical and public health significance of understanding these sex differences is critical, especially considering an aging population and the rising prevalence of coronary artery disease [4]. Reasons why women have a significantly higher risk following CABG are as follows: later onset of coronary artery disease, which is often attributed to the protective effects of estrogen in the premenopausal period [5], smaller coronary artery diameters, lower use of arterial grafts, and higher prevalence of cardiovascular risk factors, such as hypertension, dyslipidemia, and diabetes mellitus [3,6]. Consequently, these aforementioned factors might be related to the differences in clinical outcomes between both sexes and lead to poorer perioperative outcomes in women than in men.

The impact of sex difference on postoperative outcomes in patients undergoing off-pump coronary artery bypass (OPCAB) surgery remains a matter of debate. This has led to a knowledge gap, with conflicting results in the existing literature. For instance, various studies demonstrated that female sex was associated with worse postoperative outcomes in patients undergoing OPCAB surgery [7,8]. On the other hand, it was found that sex difference did not affect postoperative outcomes following OPCAB in other studies [6,9,10]. However, to the best of our knowledge, particularly in the elderly patient population undergoing OPCAB, the impact of sex difference on postoperative outcomes has never been studied in the existing literature. This study, therefore, was designed to be the first to specifically evaluate the impact of patient sex on early postoperative outcomes, including mortality and major morbidity, in an exclusively elderly population (≥70 years) undergoing OPCAB surgery.

Material and Methods

STUDY POPULATION AND DESIGN:

Between January 2013 and December 2020, a total of 1547 patients underwent elective isolated OPCAB surgery. Of these, 1219 patients were excluded based on the criteria outlined below. Among the remaining patients, 328 (21.2%) were aged 70 years or older, and they were included in this retrospective observational cohort study. The patients were divided into 2 groups according to the patients’ sex. Group 1 (women) consisted of 102 patients, while group 2 (men) consisted of 226 patients. The patients’ basic demographic and clinical characteristics, operative data, and postoperative outcomes and complications were screened, analyzed, and then compared between the groups (Figure 1). Data collection was conducted using the hospital’s electronic medical records and surgical database.

For the study, primary outcome was early-term (30-day) mortality, while secondary outcomes were lengths of intensive care unit (ICU) and hospital stays, blood transfusion requirement, and complications. Patients under 70 years old, patients whose medical data could not be accessed, patients converted to cardiopulmonary bypass during the operation, and patients undergoing emergency surgery, redo surgery, and concurrent cardiac or non-cardiac surgery were excluded from the study.

There were no missing data for the primary and secondary outcomes analyzed in this study. For baseline characteristics, cases with significant missing data were excluded from the initial cohort. Due to the retrospective nature of the study, baseline characteristics were compared, to identify potential confounders. As shown in Table 1, aside from height and smoking status, the groups were well-matched for major preoperative comorbidities, minimizing the impact of confounding on the primary outcomes. Therefore, a multivariable adjustment was not performed.

ETHICAL CONSIDERATIONS:

The study protocol was approved by the local ethics committee. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki. Due to the retrospective nature of the study, the requirement for individual informed consent was waived by the ethics committee.

SURGICAL PROCEDURE:

All patients were operated via standard median sternotomy under general anesthesia. The great saphenous vein and internal mammary artery were the most commonly used bypass grafts. To achieve a target activated clotting time >350 s, 150–200 IU/kg unfractionated intravenous (i.v.) heparin was administered. In most of the patients, a left internal mammary artery graft was anastomosed to the left anterior descending artery, while a great saphenous vein graft was anastomosed to the circumflex artery and right coronary artery, or their branches. During distal coronary anastomoses, to provide proper position at beating heart, the Octopus tissue stabilizer was used routinely, and the Starfish stabilizer was used if necessary. After an arteriotomy was performed on the coronary artery to be anastomosed, to provide a blood-free area, proximal coronary blood flow was occlused by bulldog clamps, or the intracoronary shunt was inserted based on the patients’ requirement. In addition, air blowing was routinely applied for the optimal visualization of coronary arteries. Distal anastomoses were performed with 7/0 propylene stitches, and proximal anastomoses were performed with 6/0 propylene stitches. After completing all the anastomoses, heparin was neutralized by protamine administration i.v., and then the procedure was completed in the standard fashion. All procedures were performed by the same surgical team.

POSTOPERATIVE FOLLOW-UP:

All patients were followed up for early-term outcomes until discharge or for 30 days postoperatively. All patients were transferred to the ICU following the surgery. Cardiac rhythm, invasive arterial and central venous pressures, fingertip oxygen saturation, amount of mediastinal tube drainage, and urine output were continuously monitored, and arterial blood gas analysis was conducted at frequent intervals during the ICU follow-up. Within the first 4 to 6 h following the surgery, the patients were weaned from the mechanical ventilator if they were hemodynamically and neurologically stable. Within the first 24 h following the surgery, 100 mg oral acetylsalicylic acid, 75 mg oral clopidogrel, and subcutaenous low-molecular-weight heparin were administered if not contraindicated. Patients whose hemodynamic parameters were stable were transferred to the acute inpatient ward from the first postoperative day.

In the ward, daily clinical evaluations were performed, wound care was provided, and mobilization was encouraged. Patients were typically discharged after achieving stable clinical status, adequate pain control, and no signs of complications.

STATISTICAL ANALYSIS:

All data were analyzed using the Statistical Package for Social Sciences program version 24 (IBM Corp, Armonk, NY, USA). Continuous variables with normal distribution were analyzed using the t test, while those with abnormal distribution were analyzed using the Mann-Whitney U test. Categorical variables were analyzed using the chi-square test. Continuous variables with normal distribution are presented as mean±standard deviation, while those with abnormal distribution are presented as median (min–max). Categorical variables are presented as number and percentage. A P value <0.05 was regarded as statistically significant.

Results

The study population included a total of 328 patients aged 70 years and older, and 102 (31.1%) of them were women. The mean age was 73.6 years for women and 73.8 years for men. Women were significantly shorter and had a lower smoking rate than men. In terms of other demographic characteristics and comorbid diseases, there were no significant differences between the women and men groups (Table 1).

When operative data of the patients were compared between the groups, no significant differences were detected, and the groups were similar (Table 2).

Analysis of postoperative outcomes showed that women had significantly longer durations of ICU (P<0.001) and hospital stays (P<0.001) than did men. Of the postoperative complications, only wound infection occurred at a significantly higher rate in women than in men (P=0.001).

Other postoperative outcomes and complications, including myocardial infarction (P=0.94), cerebrovascular event (P=0.98), and in-hospital mortality (P=0.91), were similar between the 2 groups (Table 3).

Discussion

The present study revealed that, although there were significant differences between the sexes in terms of the lengths of ICU and hospital stays and frequency of wound infection, sex difference had no significant impact on early-term outcomes in elderly patients undergoing OPCAB surgery, due to the fact that there were no significant differences in terms of the mortality and major complications between the sexes.

Coronary artery disease is known as a male-dominated disease. However, it can also be seen frequently in women, especially in the postmenopausal period, and is one of leading reasons of mortality in the female population. Coronary artery disease has been reported to be responsible for 1 in 3 female deaths in the United States [11]. Currently, CABG is performed as an efficacious therapeutic method in female patients with coronary artery disease, and approximately 30% of patients undergoing CABG are women [3]. Mortality and morbidity rates following CABG have been reported to be higher in women than in men [1,2]. In the most commonly used surgical risk scoring models, such as the Society of Thoracic Surgeons score and European System for Cardiac Operative Risk Evaluation Score, female sex has been included as a significant risk factor in predicting mortality following CABG [12].

However, studies investigating the impact of sex on outcomes in patients undergoing OPCAB have revealed conflicting results, and thus it has become a controversial issue whether sex difference affects outcomes of OPCAB surgery. There are many studies in the literature investigating the impact of sex difference on the early-term outcomes of OPCAB surgery. Our findings partially align with the those by Patel et al [13], who also found longer hospital stays and more sternal wound infections in women across all age groups, but contrast with results by Emmert et al [7], who reported a composite endpoint being significantly worse in women. Conversely, Puskas et al [14] analyzed a large cohort including 4492 patients (1381 women and 3111 men) undergoing OPCAB and found similar outcomes between the sexes in terms of death, stroke, myocardial infarction, and major adverse cardiac events. Our study was conducted only in elderly (70 years and older) patients undergoing OPCAB. We could not find any study in the literature investigating the impact of sex difference on perioperative outcomes in an elderly patient group undergoing OPCAB; thus, we could not compare the results of our study population with the results of similar studies.

When studies investigating the impact of sex difference on long-term outcomes after OPCAB surgery are evaluated, it is seen that the relevant issue is also a controversial area with conflicting results. For example, Cartier et al [8] found significantly lower long-term survival rates in women than in men. In contrast, Urbanowicz et al [15] revealed that the survival rate was significantly higher in women than in men. On the other hand, Fu et al [16] revealed no significant difference in survival between women and men treated with OPCAB. In our study population, we did not analyze the long-term outcomes of patients undergoing OPCAB.

Increased resource utilization in patients undergoing CABG has been considered as a significant problem, and efforts to reduce the resource utilization have gradually increased and become one of the most popular issues [17]. Female sex is known to be a predictor of increased resource utilization following CABG [18,19]. Scott et al [20] specifically examined whether patient sex affected resource utilization in patients undergoing OPCAB and demonstrated that female sex was a predictor of increased blood transfusion and longer length of stay. In our study population consisting of elderly patients undergoing OPCAB, the lengths of ICU and hospital stays in the postoperative period were significantly longer in women than in men. On the other hand, need for blood transfusion was also greater in women; however, the difference between women and men was not statistically significant.

Although our study showed no significant difference in mortality, the findings of significantly longer ICU and hospital stays and a higher rate of wound infections in women have important clinical implications. These disparities suggest an increased utilization of healthcare resources for female patients, potentially leading to higher costs [21]. The prolonged recovery trajectory for women can also impact their quality of life after surgery and delay their return to daily activities [22]. Although our study did not assess long-term outcomes, a higher incidence of postoperative complications, such as wound infections, could potentially be associated with poorer long-term morbidity. These results highlight the need for investigating potential underlying causes and developing targeted postoperative care strategies to mitigate these sex-based disparities in elderly patients undergoing OPCAB.

The main limitations of the study were its single-center, retrospective design, relatively small sample size, and limited data analysis. The small sample size may have prevented us from detecting smaller, yet clinically relevant, differences in some complication rates. Furthermore, the lack of long-term follow-up results is an important limitation that precludes any conclusions on survival beyond the early postoperative period.

Conclusions

To the best of our knowledge, the present study is the first clinical research investigating the impact of sex difference on early postoperative outcomes in an elderly patient population (70 years and older) undergoing OPCAB surgery. Our study revealed for the first time in the literature that, even though women experienced increased resource utilization as evidenced by significantly longer ICU and hospital stays and a higher rate of wound infection, sex difference did not have a significant impact on major early-term adverse outcomes, such as mortality and major organ system complications, in elderly patients undergoing OPCAB surgery. This suggests that while women may have a more challenging initial recovery, the OPCAB procedure itself can be performed with comparable safety in elderly men and women. However, further prospective well-designed studies with larger patient participation are required to support the results of the present study and obtain more precise scientific evidence.