Discussion
This study is the first to review current practice of UK national data to compare sex-related differences in outcomes following surgical coronary revascularisation and valvular cardiac procedures.
From our dataset of 210,155 patients (25.7% female), we found female sex to be an important risk factor for 30 day mortality following CABG, AVR and MVR. Following CABG, female sex was also associated with increased post-operative need for dialysis, deep sternal wound infections and length of hospital stay.
The present study supports the well reported claim that females undergoing coronary revascularisation surgery are often older and with more comorbidities than males (3). Furthermore, we found that women were also more likely to need urgent, as opposed to elective, revascularisation than men, which may be responsible for some of the poorer outcomes reported.
It is also suggested that sex-related differences in operative strategy decisions and techniques may explain sex-related differences in cardiac surgery outcomes (14). For example, a higher proportion of males compared with females received LIMA, RIMA or BIMA grafting in both our cohort and other studies (15) which is suggested to predispose females to incomplete myocardial revascularisation (16,17). Nevertheless, the multivariable regression analysis used in our study adjusted for differences in baseline and operative differences, including revascularisation strategy and still a sex-related difference remained in short-term mortality. These findings suggest that female sex is an independent risk factor for short-term mortality following CABG which supports the consensus of the current literature (6,18). The idea of female sex being an independent risk factor for worse outcomes following CABG is speculated to be related to the more challenging anatomy of female patients, such as smaller coronary artery targets for grafting, narrower conduits and more diffuse patterns of coronary disease (3,19).
Our study also evaluated other post-CABG outcomes. We did not find an increased risk of stroke following CABG as other national studies have reported (8, 20). This may be related to the fact that in our cohort of females a significant 15% underwent off pump revascularisation which has been reported to be particularly beneficial in women because of its effect to reduce the risk of stroke (21).
Sternal wound complications were more common in females than males following CABG in our study. A risk prediction tool developed in the UK identifies female sex as one of six independent predictors of surgical site infection following cardiac surgery (22). The B-SIR score also includes raised body mass index >30, diabetes, left ventricular ejection fraction <45% and peripheral vascular disease; all of which were more common in our female patients. This finding may indicate a complex multifactorial impact of female sex on the risk of developing wound complications. This would suggest that efforts to prevent SSI should aim to target all of the these modifiable risk factors, especially in our female patients.
While the majority of patients who underwent CABG were male, single valve surgery was more evenly distributed between the sexes. In contrast to CABG, females were more likely to have a planned elective valve procedure. Despite this, female sex was associated with significantly higher short-term mortality following both isolated AVR and MVR procedures.
Our finding of increased mortality following AVR in females is reflected from other nationally representative databases such as United States of America (23) and a previous UK database analysis (24). However, other national studies did not report sex-related differences in AVR mortality (12, 25).
In our study, men were more likely to receive a mechanical aortic valve than women which may reflect the differences in age and comorbidities between the sexes at time of surgery and their influence on the management planning. It is known that women with severe aortic stenosis are diagnosed at a later stage of the disease process (26) but even when adjusting for pre-operative difference women are less likely to be referred for surgical AVR than men (27, 28).
There is no clear explanation for why women have worse outcomes compared to men following AVR but several mechanisms have been implicated. For similar degrees of aortic stenosis, females tend to have higher transvalvular pressure gradients, thicker ventricle walls and smaller end-systolic and end-diastolic chamber sizes than males (29). Secondly, females on average receive smaller valves than males, the outcomes of patient-prosthesis mismatch (PPM) seem more severe in smaller size valves (30) and therefore may effect women disproportionately. Furthermore, females are also more likely to require additional aortic annular enlargement than males leading to increased operative risk associated with the annular enlargement procedure (5).
As with the other procedures, females in the UK experienced an increased odds of 30-day mortality following MVR than males. A 2013 study of 3,761 patients found a difference in mitral pathology between males and females undergoing mitral surgery; males were more likely to have mitral valve leaflet prolapse whereas females were more likely to have calcified mitral valve leaflets (31). This differences in pathology explains why females are more likely to need a mitral valve replacement whilst males are more likely to receive a mitral valve repair, a finding reiterated in our study. A study of MV procedures from USA, 2000-2009, also agreed men were more likely to receive a MV repair than women (32). This difference in surgical management strategy is thought to contribute to the poorer outcomes we see in females (33).
Interestingly, for both CABG and AVR surgery, female sex seemed to be protective for post-operative bleeding resulting in returning to theatre. Oestrogen has a pro-coagulant effect which may confer benefit to limit post-operative bleeding (35). Despite females tending to have lower rates of returning to theatre for bleeding, females have been shown to receive more post-operative red blood cell transfusions with males and this is associated with delayed recovery (10).