Longevity is increasing in many countries, where life expectancy at birth is rising [1]. A reduction in mortality among older age groups seems to be one of the main reasons for this increase [2], and consequently, living with chronic, incurable diseases is becoming more frequent [3]. Population aging, improved public health policies, and advances in cardiovascular disease prevention and treatment have increased the number of people living with chronic disease because more individuals survive acute cardiovascular events, increasing the prevalence and absolute number of older adults living with these conditions and their complications [4]. This compromises the quality of life of these individuals and highlights the concept of frailty, which is gaining prominence in clinical practice [5]. Frailty is the physiological decline of the body’s functional reserves [5,6].

Aging-associated frailty increases the risk of postoperative complications, and age and frailty are recognized as risk factors for mortality and morbidity in patients undergoing surgical procedures [5,7,8]. Coronary artery bypass grafting (CABG) is a well-established, common procedure; specifically, 169,705 operations were performed in 2020 in the United States and 19,125 procedures in Brazil’s Unified Health System in 2023 [9,10]. Given these figures, it is essential to consider the morbidity associated with this procedure and seek better clinical outcomes and quality of life for patients.

Among the postoperative complications that arise within 30 days, surgical site infection (SSI) stands out for its clinical relevance, occurring in 0.3% to 3.5% of myocardial revascularization cases [11-16]. The associated mortality rate varies from 10% to 47% in cases of SSI, significantly contributing to an increase in morbidity, mortality, and hospital costs and potentially trebling the procedure’s cost and having a considerable impact on public resources [15,17-19].

SSI is associated with worse short- and long-term clinical outcomes. Interestingly, age alone does not seem to be a relevant predictive factor for this outcome [20-22]. Moreover, frailty has not been properly investigated as a possible risk factor for SSI in patients undergoing myocardial revascularization.

It is well established that frailty increases morbidity and mortality in older adults as well as the risk of postoperative complications by up to 2.54 times [5,7]. Therefore, it is plausible that individuals with frailty may be more susceptible to SSI than the general population. There may be additional factors associated with this potential increase in risk, which, if identified, will facilitate the development of specific preventive strategies for this patient population.

The objective of this study was to identify the perioperative variables associated with SSI in patients with frailty and prefrailty undergoing CABG within 30 days after surgery.

The sample consisted of 467 patients, 26 (5.6%) of whom had SSI. The classification of the type of SSI was as follows: 1.9% (n=9) sternal dehiscence, 1.5% (n=7) superficial SSI, 1.1% (n=5) deep SSI, 0.4% (n=2) deep infection with use of corticosteroids, 0.4% (n=2) mediastinitis, and 0.2% (n=1) subtype not specified in the database (Table 1). The classification of “deep infection with corticosteroid use” reflects the original FRAGILE dataset subtype classification; subtype categories were reported descriptively only and were not used in the univariable or multivariable models.

Table 2 shows the results related to the preoperative variables associated with SSI.

The median age was similar between the groups with and without infection (70, IQR 65‐74 vs 69, IQR 65‐74 years, respectively; P=.79), as was the median BMI (28, IQR 24‐33 vs 26, IQR 24‐29 kg/m², respectively; P=.07). Between the 2 groups, there were no statistically significant differences in sex (male: 14/26, 53.8% vs 303/441, 68.7%, respectively; P=.12), presence of diabetes mellitus (10/26, 38.5% vs 153/441, 34.7%, respectively; P=.70), or creatinine clearance (median 63, IQR 48‐82 vs 62, IQR 51‐76 mL/min, respectively; P=.91).

However, there was a significant association between NYHA functional class and the occurrence of infection (P=.02), with a higher proportion of patients in class IV in the group with infection (7/26, 26.9% vs 31/441, 7.0%; Figure 1). The CCI was higher among patients with infection (median 5, IQR 4‐6 vs 4, IQR 3‐5; P=.01; Figure 2). The frailty score was slightly higher in the infection group than in the group without infection but without statistical significance (median 4, IQR 3‐5 vs 4, IQR 3‐4, respectively; P=.49). Table 3 shows the results obtained for the intraoperative variables.

The number of mammary arteries used also showed no statistically significant difference between the infection and no infection groups (P=.52; ie, using only 1 mammary artery [20/26, 76.9% vs 298/441, 67.6%, respectively] or using 2 mammary arteries [6/26, 23.1% vs 133/441, 30.2%, respectively]). The use of CPB was more frequent in the group with SSI (21/26, 80.8% vs 223/441, 50.6%; P=.003; Figure 3). CPB time was statistically associated with SSI in univariable analysis (median 85, IQR 71‐128 vs 85, IQR 65‐105 minutes in the infection and no infection groups, respectively; P=.02). Although the medians were identical, the distribution differed between groups (IQR shift), and this finding should be interpreted cautiously. Additionally, the total time of the surgical procedure was different between the groups, with prolonged surgery time being associated with a higher occurrence of infection (median 303, IQR 250‐359 vs 270, IQR 217‐325 minutes in the infection and no infection groups, respectively; P<.001). Table 4 shows the results obtained for the postoperative variables.

Occurrence of bleeding was higher in the group with infection (2/26, 7.7% vs 4/441, 0.9%; P=.04). The duration of mechanical ventilation was significantly longer among patients with infection (median 18, IQR 8‐21 vs 8, IQR 5‐14 hours; P=.001), as were the total length of hospital stay (median 41, IQR 23‐55 vs 7, IQR 6‐11 days; P<.001) and the length of ICU stay (median 5, IQR 4‐15 vs 3, IQR 2‐5 days; P<.001). The need for reoperation was considerably more frequent in the group with infection (13/26, 50% vs 13/441, 2.9%; P<.001).

In the multiple logistic regression analysis, 2 variables were identified as independently associated with SSI (Table 5). All 467 patients were included in the multivariable regression.

The CCI was associated with the outcome (OR 1.58, 95% CI 1.25‐1.99; P<.001), indicating a 58% increase in the likelihood of infection with each additional point on the index. The use of CPB also proved to have a significant association (OR 4.89, 95% CI 1.71‐13.94; P=.003). The model showed good discrimination, with an area under the receiver operating characteristic curve of 0.752 (95% CI 0.662‐0.842; P<.001; Figure 4).

In this study, an SSI rate of 5.6% (26/467) was observed in patients with frailty undergoing myocardial revascularization. Although this was higher than the rates reported in previous studies [16,20-22], no study has addressed frailty in a population like the one we studied. Among the factors analyzed, the CCI and the use of CPB were identified as associated with SSI, especially CPB, which was independently associated with higher odds of SSI.

The association between frailty and adverse outcomes in surgery has been widely described. Studies have shown that patients with frailty have a higher risk of mortality, prolonged hospitalization, and infection complications [5,7,26]. In this study, even after adjusting for other variables, the CCI was significantly associated with the occurrence of SSI (OR 1.58, 95% CI 1.25‐1.99; P<.001), which demonstrated that the accumulation of comorbidities associated with a decline in physiological reserves increases the association with SSI by 58% for each 1-point increase in the CCI. We additionally clarified how frailty was operationalized in the cohort and how its distribution may have limited discrimination within an already frail population.

The frailty score did not discriminate SSI risk within this cohort, likely because participants were selected for frailty and prefrailty by design, reducing variability in frailty burden and limiting discrimination for this end point. Rather than functioning as a within-cohort predictor, frailty in this study should be viewed as a biological substrate of vulnerability potentially linked to reduced immune responsiveness and diminished physiological reserve that may contribute to the susceptibility to SSI. Consequently, additional perioperative factors may better explain variation in SSI occurrence among patients already meeting frailty and prefrailty criteria.

The use of CPB also showed a significant association with infection, corroborating the literature that associates CPB with greater systemic inflammatory activation, increased tissue permeability, and transient immune suppression [27,28]. The same trend was observed for CPB time, which differed between the groups. The use of this technique and the intensity of the associated stress are important markers of operative complexity and greater exposure to infectious risks. Mechanistically, CPB is associated with complement activation and cytokine release, endothelial and glycocalyx injury, and transient immune dysfunction, which may impair wound healing and facilitate infection in vulnerable patients.

Reoperation was strongly associated with SSI in the unadjusted analysis. However, because reoperation was recorded after CABG and its temporal relationship with SSI diagnosis was not reported, it should be interpreted as a postoperative correlate rather than as a predictor of SSI. This finding corroborates those of studies showing that surgical revision, especially at an early stage, compromises anatomical barriers and favors colonization of deep tissue of the thorax [29]. Additionally, patients who require reoperation often have more severe clinical profiles and are subject to repeated stressors, including the use of invasive devices for prolonged periods.

Although variables such as age, BMI, and diabetes mellitus have traditionally been related to sternal infection [16], they did not prove to be significant in this study. This result appears to be associated with the fact that the analysis was specific to a population with frailty, in which factors associated with a drop in physiological reserve are more prominent.

Other relevant variables were NYHA functional class and length of mechanical ventilation, which were significantly associated with infection, similar to what has been described in the literature [17,30,31]. More advanced functional classes, such as NYHA class IV, showed a higher association with infection, possibly because they reflect greater previous hemodynamic compromise. This leads to longer intubation time in the postoperative period, which can hinder healing and predispose patients to infection.

The number of mammary artery grafts used did not influence the occurrence of infection; however, there are studies that demonstrate an increase in incidence when 2 mammary grafts are used [32,33]. The results of our study may encourage surgeons, when choosing grafts, to use a greater number of mammary grafts because of the benefit of durability and because the complications of SSI are similar whether one or more is used.

Length of hospital and ICU stay were associated with a higher occurrence of SSI, which indicates a negative cycle in which longer hospital stay increases the association with infection and the occurrence of infection increases the length of hospital stay. Longer hospital stays are associated with longer use of invasive devices, more contact with hospital pathogens, and changes in the patient’s microbiota. In turn, the occurrence of infection contributes to an increase in hospital admissions, the use of antibiotics, the need for procedures secondary to infection, and delay in postoperative recovery. Consequently, guidelines associated with multiple actions have emerged with the aim to reduce the length of hospital stay and, subsequently, reduce the occurrence of SSI [34].

Makary et al [7] suggested incorporating frailty score into the set of risk predictors commonly used in clinical practice. Risk assessment in cardiovascular surgery is carried out using scores such as the EuroSCORE and the Society of Thoracic Surgeons score, which estimate risk without considering the decline in the individual’s physiological reserves. The inclusion of the frailty score and prior assessment of comorbidities during the evaluation contribute to the early identification of patients who are more susceptible to complications, allowing for preventive actions through adjustments to the surgical technique, preoperative preparation of the patient’s physical condition, and strict control of comorbidities.

This multicenter study used standardized criteria for assessing frailty and multivariable logistic regression, which showed that the CCI and CPB use were independently associated with SSI. Preoperative recognition of patients with frailty with a high number of comorbidities, especially those undergoing CPB, can guide prevention strategies and more intensive monitoring in the pre- and postoperative periods.

However, this study had some limitations. The number of SSI events was relatively small, which may have limited the stability of the multivariable model and increased the risk of overfitting. The retrospective use of medical records from multiple centers may have resulted in variation in the completeness and consistency of documentation for certain clinical variables, particularly SSI subtype, microbiological findings, and antibiotic treatment. Because of the limited number of SSI events, we did not adjust for center-level effects, and residual confounding due to interinstitutional variation in perioperative care and SSI surveillance cannot be excluded. The composite SSI end point included events with different clinical severity (superficial infection, deep infection, mediastinitis, and dehiscence). Because of the limited number of events in each subtype, we were unable to perform robust subtype-specific modeling; thus, associations may differ across SSI phenotypes. We assessed discrimination (area under the receiver operating characteristic curve) but did not formally evaluate model calibration; therefore, the clinical applicability of predicted risks should be interpreted cautiously. Although CPB assignment was randomized in the parent trial, the present analysis included only centers with complete eligible data; therefore, postrandomization exclusions and center selection may have introduced selection bias and limited generalizability. We did not formally quantify multicollinearity using the variance inflation factor or correlation coefficients; therefore, residual collinearity among operative variables cannot be excluded.

We conclude that factors such as NYHA functional class IV, CCI, CPB time, bleeding, duration of mechanical ventilation, need for reoperation, use of CPB, and length of hospital and ICU stay showed an unadjusted association with SSI. Additionally, we demonstrated that the CCI and the use of CPB were independently associated with SSI in the multivariable model within 30 days after CABG.