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From the Department of Cardiothoracic Anesthesia and Outcomes Research, Cleveland Clinic, Cleveland, Ohio.
Address correspondence and reprint requests to Colleen Gorman Koch, MD, MS, FACC, Departments of Cardiothoracic Anesthesia (G-3), Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44122. Address e-mail to kochc{at}ccf.org.
Although the DNA sequence of the human X chromosome may explain observed gender differences in response to disease processes,1 it is questionable whether gender differences translate into significant outcome differences necessitating a paradigm shift for care of female cardiac surgical patients. The age for diagnosis of coronary artery disease differs between women and men, as well as sensitivity and specificity of some diagnostic imaging tests. However, given that a female patient has defined cardiovascular disease and is presenting for surgery, what, among published investigations, behooves one to consider a gender-specific paradigm of care?
Furthermore, what would a perioperative gender-specific paradigm of care look like? A paradigm shift calls for something that is fundamentally different in terms of management. When patients present to surgery, we perform similar physical examinations, order similar panels of laboratory tests, and aim to optimally control comorbid conditions, regardless of whether a patient is male or female. Our focus is on specific physiologic variables that are patient- and disease-based rather than gender-based.
This commentary will focus on patients with cardiovascular disease presenting for surgery. Preoperative evaluation and diagnosis of coronary artery disease may necessitate gender-specific considerations; however, it is this author’s opinion that the perioperative period should focus on management of an individual patient’s risk factors known to be associated with adverse outcome, rather than development of separate gender-specific care paradigms.
GENDER PROFILES
Increased unadjusted morbidity for women after cardiac surgery is a common finding among published investigations. At baseline, the profile of the female patient undergoing surgery is certainly different from men. Demographics, laboratory values, clinical presentation, and sets of comorbid conditions consistently demonstrate that women come to surgery with more risk factors than do men.2–7
When variables are modeled to statistically predict whether a patient is female, shorter height, increased weight, more hypertension, insulin-treated diabetes, and history of heart failure are among the variables that best differentiate female from male patients. Females have been further characterized by higher high-density lipoprotein levels, increased triglycerides, and reduced red blood cell mass. Male patients are more often smokers, consume alcohol, have reduced left ventricular ejection fraction, and have more extensive left main and circumflex coronary artery disease.8
Prior studies have described greater disabling symptoms in women, such as higher New York Heart Association functional class and Canadian Cardiovascular Society Classifications,3,9 despite less extensive coronary artery disease2,10 and better preserved ejection fractions compared with men,2,10 which complicates the notion of delayed referral for surgery in women.
Female gender may represent a marker for higher risk, as women tend to come to surgery with a disproportionate distribution of risk factors associated with morbid outcomes after cardiac surgery.2–7,11 It is important to note that these risk factors are not gender-specific; they are also prevalent in men and place patients at increased risk regardless of gender.
OUTCOMES
Survival
Higher risk-adjusted morbid outcomes for women undergoing cardiac surgery is certainly not a consistent finding among published investigations.3,4,10 There is continued debate regarding whether greater early mortality among women after bypass surgery is attributable to presenting risk factors or gender per se. Some investigations report higher adjusted early mortality for women,6,12–14 whereas others report similar mortality outcomes.3,5,10,15 Evidence gathered from studies examining gender-related differences in long-term survival after hospital discharge has also been equivocal.4,6,13,16,17
An editorial entitled "Is it Gender, Methodology or Something Else?"18 explored whether unaccounted biologic factors, statistical methodology, or failure to capture process-of-care variables affected short-term outcome differences between women and men. From a database management perspective, failure to capture details on comorbidity and clinical presentation, lack of standardized definitions and a failure to capture process-of-care decisions all contribute to variability in results among cohort investigations. For example, Guru et al.6 reported higher early mortality for women after coronary artery bypass graft (CABG); however, when they examined a subset cohort of patients who had a complete set of data on body surface area measurements and included it in the statistical modeling, female gender was eliminated as a risk factor for 30-day mortality. Thus emphasizing that a complete data set of variables and appropriate risk-adjustment techniques should be considered when evaluating investigations on gender and outcomes.
Process-of-care decisions in the perioperative period exhibit considerable variability among individual surgeons and institutions for which there is often no accounting or measurement. There is significant variability in process-of-care decisions such as completeness of revascularization (women less complete revascularization),9,10,17 use of arterial conduits,9,17 and transfusion of blood products (women receive more blood transfusions).3 Benefits of internal thoracic artery conduits confer both short- and long-term survival benefits,19–21 and these grafts have previously been less commonly used in the female patient.9,17 Red cell transfusion is a factor that increases risk in a dose-dependent manner for almost all morbid outcomes after cardiac surgery.22 When similarly matched on perioperative variables, including preoperative blood volume estimates, women have been reported to receive more red cell transfusions than men.3 These important process-of-care decisions significantly modulate morbid risk for both women and men after cardiac surgery. Women are clearly placed at a disadvantage by the operative strategy, rather than developing a gender-specific care paradigm, perhaps, women should be treated more like men.
Furthermore, separate gender-specific management strategies may not be practical in the perioperative period. Rather than making a gender-specific protocol for management, increased focus should be on better perioperative management of risk factors similar to both women and men. For example, although there is some biologic variability in pharmacologic response between women and men for specific medications, much of the pharmacologic intervention is directed at well-defined target end-points. Antihypertensive medications are adjusted for specific systolic and diastolic end-points; statins are adjusted for lipid profile end-points; insulin and oral diabetic medications are targeted to specific plasma glucose or hemoglobin A 1C measurements. Each management decision is individualized regardless of gender.
With regard to the intraoperative period, there is insufficient information to determine whether proposed biologic differences in response to drugs influence outcome. Our intraoperative monitors allow us to titrate medications beyond simple body weight specifications: the bispectral index monitor allows one to titrate anesthetics to specific target end-points; intraoperative drugs such as β blockers and antihypertensives may be titrated to appropriate end-points for heart rate and arterial blood pressure; inotropic drugs can be targeted to cardiac output measurements. Unique gender differences in pharmacologic response have not been demonstrated to result in measurable perioperative outcome differences. Subtle gender differences in pharmacologic response, if clinically meaningful, are managed with usual intra- and postoperative techniques and are likely overshadowed by preoperative comorbidities.
Beyond Survival
In general, women report less satisfactory symptomatic relief, less functional recovery, and lower quality of life after CABG.7,23,24 These patient-centered outcomes are important as they reflect the patient’s perception of their quality of life. The proposed reasons for these findings have included less complete revascularization,9,10 fewer internal thoracic artery grafts,9,15,17 and less referral to and participation in cardiac rehabilitation programs for women after surgery.25 The factors again represent process-of-care decisions involved in the care of cardiac surgical patients and are differentially applied to gender.
Interestingly, Kurlansky et al.15 reported that men and women undergoing CABG using bilateral thoracic artery grafts had similar quality of life and comparable operative morbidity and early and late survival. The authors commented that reported gender differences in outcomes from prior investigations were perhaps related to less frequent internal thoracic artery conduit use in women.
Participation in cardiac rehabilitation programs exerts an important influence on recovery after cardiac events and surgery through exercise training and instruction on life-style modification.26–28 In addition, short-term cardiac rehabilitation has been shown to positively influence quality of life scores for both women and men.29 Caulin-Glaser et al.25 reported that women were less likely than men to be instructed on secondary prevention strategies or referred to cardiac rehabilitation after revascularization procedures. Less frequent participation in cardiac rehabilitation may be reflected in lower functional quality of life for women after surgery. An increased emphasis should be placed on investigating why there is less referral and participation in cardiac rehabilitation for women. Again, this relates to a process-of-care being differentially applied to women and men, rather than gender per se.
Future Directions
Focus in the perioperative period should be on better management of well-defined risk factors for morbid outcomes. Gender, as it relates to these risk factors, certainly necessitates further investigation. The impact of perioperative process-of-care decisions on outcomes, such as use of arterial grafts and transfusion practices and gender differences in quality of life with under-utilization of cardiac rehabilitation services, deserves more attention. At this time, it is difficult to suggest a paradigm shift when the basis for one is yet unknown. If men and women were treated similarly, would there be a reason to shift the paradigm?
Canto et al.30 recently addressed the question of whether a separate gender-based symptom evaluation for women with acute coronary syndromes (ACS) should be put forth. The authors suggested that age may be a more important contributor to differences in ACS presentation among women and men because older age has been associated with fewer reports of chest pain. Women are older than men when they present with ACS and this may be associated with their symptom presentation rather than gender per se. The authors recommended that the current symptom message, which targets women and men equally, should remain unchanged.30
CONCLUSIONS
Gender differences in preoperative profiles for patients undergoing cardiac surgery have been well-recognized. Gender differences in terms of why and when specific care decisions are made need to be recognized for their differential application and contribution to increased morbid risk; women are clearly placed at a disadvantage from this standpoint. Differences in presentation do not translate into a need for gender-specific treatment plans, specifically in the perioperative period. It is difficult to propose a gender-specific paradigm shift for perioperative management of something so ill-defined; rather, it is more prudent to manage risk factors and process-of-care variables known to exert influence on outcomes for individual patients, regardless of gender, after surgery. The pursuit of as yet unidentified biologically driven paradigm shifts leads one away from the obvious need to apply proven perioperative strategies broadly to women and men who present with equal-opportunity comorbidities.
Footnotes
Accepted for publication January 28, 2008.
REFERENCES
This article has been cited by other articles:
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  K. Gelb and A. W. Gelb Sex and Gender in the Perioperative Period: Wake Up to Reality Anesth. Analg., July 1, 2008; 107(1): 1 - 3. [Full Text] [PDF]
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