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Ann Thorac Surg 2001;71:521-530
© 2001 The Society of Thoracic Surgeons
a Department of Cardiovascular Surgery, St. Vincent Mercy Medical Center, Toledo, Ohio, USA
b Department of Cardiovascular Surgery, Medical College of Ohio, Toledo, Ohio, USA
Accepted for publication May 20, 2000.
Address reprint requests to Dr Habib, Cardiopulmonary Research, St. Vincent Mercy Medical Center, 2213 Cherry St, ACC Bldg, Suite 309, Toledo, OH
e-mail: robert_habib{at}mhsnr.org
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Abstract |
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Methods. A total of 3,560 consecutive patients undergoing coronary artery bypass grafting from 1991 to 1997, including 2,401 (67%) males and a mean ± SD age of 63 ± 10 years were ranked based on their body mass index (BMI). The association in these patients of preoperative, long-term, and economic data with variations in BMI were studied using regression analyses. Long-term survival was studied using 5-year Kaplan-Meier survival analysis.
Results. Operative mortality, myocardial infarction, cerebrovascular accidents, blood transfusions, and length of hospital stay were all increased in the smallest patients (BMI 
24 kg/m2). Obesity did not increase adverse operative outcomes except for a greater rate of sternal wound infections occurring with increasing severity of obesity. Direct variable costs were lowest in patients clustered around normal BMI, with cost increasing similarly at low and high extremes. This effect was correlated with similar BMI effects on ventilatory and intensive care requirements. Excluding operative mortality, 5-year survival trends were similarly worse for the smallest (BMI 24) and most severely obese (BMI > 34) patients. Mild obesity (BMI 
30 to BMI < 34) did not affect long-term survival.
Conclusions. Among study patients, immediate operative outcomes were adversely affected by small body size, which reflected older age (66 ± 10 years) and an exaggerated adverse impact of cardiopulmonary bypass. Younger age and smaller effects of cardiopulmonary bypass lead to better operative outcomes in the obese. Long-term outcomes were, however, suboptimal in severely obese patients although that group was the youngest (60 ± 10 years). In addition to their large body habitus, other factors, including substantial prevalence of diabetes, insulin dependence and hypertension, probably played a significant role in the poor long-term outcome in the severely obese.
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Introduction |
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There is a long-standing perception that obesity increases the risk of adverse outcomes following CABG. This is perhaps due to the higher incidence of such comorbid conditions in obese patients as diabetes, hypertension, and impaired respiratory function [9–12]. Interestingly, however, several recent studies have shown equal or even reduced operative mortality (OM) in obese versus nonobese CABG patients. Those findings have largely exculpated obesity as a risk for adverse outcomes except for sternal wound infections [2, 9–12].
Indeed, a number of studies reported increased OM following CABG in patients with low body surface area (BSA, m2) compared with patients with normal or high BSA [4, 8]. Some authors have also proposed that the greater incidence of low BSA in women contributes to their worse CABG outcomes compared with outcomes in men [4, 8, 13]. A recent large single institution study examined this proposition, however, and concluded that small body size did not significantly increase in-hospital CABG mortality for either sex despite an increasing risk of postoperative low output syndrome in women [13].
The latest review of information from the The Society of Thoracic Surgeons National Cardiac Surgery Database by Edwards and colleagues [4] indicated first, that morbid obesity is an independent predictor of increased operative mortality in CABG patients, and second, that operative mortality decreases sharply in patients with median BSA values versus those with low BSA and is unchanged for those with higher BSA values. These findings are intriguing and may at first glance appear counterintuitive. The apparent contradiction is predicated on the fact that BSA is higher in obese patients and that it parallels increased body mass index (BMI defined as weight/(height)2, kg/m2) (Fig 1). Obesity is typically defined using BMI, since it is the body size measurement that best correlates with body fat content [14].
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Material and methods |
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Cardiopulmonary bypass
Cardiopulmonary bypass was performed using standard techniques. An extracorporeal circuit consisting of a membrane oxygenator (Baxter Healthcare Corp, Irvine, CA) and a centrifugal pump (Medtronic, Minneapolis, MN) was utilized. Typically, the pump was primed with 1,800 mL of Plasma-Lyte (Baxter Healthcare Corp), 50 g of mannitol (250 mL), and 50 g of albumin (200 mL). Normothermic perfusion, with a lowest core temperature of more than 35°C, was used in the majority of patients (
95%). Cardioplegia, given antegrade or retrograde, consisted of Plegisol (Baxter Healthcare Corp) with 1 g of lidocaine hydrochloride, 50 mEq of KCL, and 15 g of NaHCO3 (8.4%) in cold blood. Arterial blood flow was determined on the basis of a cardiac index of 2.5 to 3.0 (L · min–1 · m–2), and mean arterial pressure was maintained at a minimum of 60 mm Hg.
Patient outcomes
Intraoperative variables, postoperative complications, and operative mortality (OM) data were collected on each patient and entered into the cardiac surgery database. Hospitalization measures included cardiovascular intensive care unit (ICU) stay , postoperative length of stay (PO LOS) and total length of stay (LOS).
The effects of patient body size on long term outcomes were also explored. To insure up-to-date results, the U.S. Social Security Administration Death Master File was queried for every patient’s name and Social Security number as of the end of February 2000. This corresponds to a minimum follow-up of 26 months for patients enrolled December 1997 and a maximum follow-up of 104 months for patients enrolled July 1991. The cardiovascular surgery database was then updated for all deceased patients with the exact date of death. Five-year Kaplan-Meier survival plots were then determined for all patients combined and for four patient size subgroups: small (BMI 24 kg/m2), normal (BMI > 24 to 30), obese (30 < BMI 34), and severely obese (BMI > 34).
Cost of CABG
Besides LOS results, economic results in terms of patient BMI were assessed from actual CABG cost data in 628 consecutive 1997 patients [15]. Cost, defined as operative cost of care was determined as the sum of all direct variable costs during hospitalization; these encompassed every care-related cost during the entire admission obtained from the hospital’s internal accounting system. Briefly, each departmental manager with aid from the finance department calculated the labor and material costs of each item and service. Purchase prices were used for disposable items. Room costs were based on nursing labor costs (staffed at registered nurse to patient ratio of 1:1 in the cardiovascular ICU and 1:2 during days and 1:3 during nights in the cardiac step-down unit) and miscellaneous supplies, not elsewhere charged. Services, such as laboratory and radiographic tests had a direct variable cost based on the disposable supply used, such as test tubes or roentgenogram film, the labor involved in performing the service, and wear-and-tear of the equipment.
The cost of CABG in individual patients was compared with the median cost for the entire 1997 group, which was given the value of 1. Patients with costs greater than 2 standard deviations above the mean cost were considered to be outliers (n = 21).
Data analysis
Patient subgroups
The frequency of BMI values among patients undergoing CABG occurs in a near-normal distribution, with most patients clustered around the median BMI, between 28 to 29 kg/m2 (Fig 2). Continuous patient variables (eg, BMI, age), unlike dichotomous patient variables (eg, gender, diabetes), necessitate a decision as to how the patient population should be subdivided to properly determine their effect on categorical outcome measures (eg, operative mortality, stroke).
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In this study, we applied a 75% between-group overlapping scheme for consecutive decile BMI subgroups, as follows: We first ranked patients between 1 and 3,560 (0 to 100%) in terms of increasing BMI, sorting all patient data accordingly. Next, patients were divided into subgroups of equal size (NS = 356 or 10% of the entire population). The 10% or 356-patient sample size was assumed to be sufficiently large to allow meaningful within-group averaging and frequencies. A total of 37 subgroups resulted from the overlapping, such that group 1 included patients 1 to 356 (0% to 10% BMI), group 2 includes patients 90 to 445 (2.5% to 12.5% BMI), and so on (Fig 1).
Note that use of such overlapping subgroups is particularly useful when the values of the independent variable are nonuniformly distributed. Given the bell-shaped BMI distribution (Fig 2), consecutive subgroups of equal size may have grossly different ranges (and medians) unless subgroup data are overlapped. Importantly, other critical variables in patients undergoing CABG, such as age and time on cardiopulmonary bypass, are also nonuniformly distributed. The use of greater than 75% overlapping was examined, but its results did not differ from that of 75% overlapping.
Statistical methods
Univariate linear and nonlinear regression analyses (SigmaStat; SPSS, Chicago, IL) were used to determine which preoperative, intraoperative, and postoperative variables were significantly altered in relation to BMI. Long-term outcomes for BMI patient groups were assessed by Kaplan-Meier survival analysis. The significance of differences in intermediate survival (for 2-years, or 24 months) and long-term survival (5 years, or 60 months) between-groups was determined from 2 x 2 (groups) and 2 x 4 (overall) 
2 tables comparing censored versus uncensored Kaplan-Meier data (survivors versus nonsurvivors). A p value of less than 0.05 was always used to indicate significance.
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Results |
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Univariate regression results of preoperative risk factors that were significantly correlated to changes in BMI are summarized in Table 1. Patient age was significantly lower in high-BMI patients than in low-BMI patients (Fig 3A). Female patients were disproportionately represented at extremes of BMI (Fig 3B). Incidence of diabetes, insulin dependence, and hypertension were linearly increased as a function of BMI. In contrast, cerebrovascular disease, chronic obstructive pulmonary disease, congestive heart failure, left main coronary artery disease, and reduced ejection fraction (< 30%) were more prevalent in patients with low BMI. The incidence of New York Heart Association class III to V was similar at low and high BMI values; more patients at classes III to IV occurred in those groups than in patients at or near median BMI. Triple vessel disease, renal failure or insufficiency, preoperative myocardial infarction, and unstable angina were not associated with BMI.
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2%) compared with those with low BMIs (5% for the smallest patients), while only a small tendency for higher OM was seen at the highest BMI (Fig 6).
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24 kg/m2) and severely obese patients (BMI > 34 kg/m2) relative to those who are normal (BMI > 24 to 30 kg/m2) and mildly obese (BMI >30 to 34 kg/m2). Five-year survival comparisons were statistically significant overall (2, p = 0.05), for small versus normal patients (p = 0.037), and for severely obese versus normal patients (p = 0.05). This finding was unchanged when men (Fig 11B) and women (Fig 11C) were considered separately.
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Comment |
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When patients are grouped as obese and nonobese, the two subgroups are necessarily heterogeneous; each includes a wide range of body size values (based on either BMI or BSA). In our case, such a grouping would have labeled patients with BMIs between 16 and 30 kg/m2 as nonobese and labeled those with BMIs between 30 and 58 kg/m2 as obese. Such wide within-group variations in BMI may dilute or even mask the true effects of body size on outcome. Consequently, we implemented an overlapping approach that allowed a more continuous description of how variations in BMI may alter operative and economic outcomes.
Our analyses indicate a complex effect of patient body size on operative and economic outcomes of CABG. First, compared with normal-BMI patients (OM, approximately 2%), operative mortality—defined as either in-hospital or out of hospital death within 30 days of surgery—is significantly higher in the smallest patients (BMI approximately 5%) but not for the obese (Fig 6). Similarly, postoperative stroke and myocardial infarction were increased in low-BMI patients only (Figs 8A, 8B). Conversely, sternal wound infections were not increased in those with a low BMI and were increasingly more prevalent with increasing levels of obesity (Fig 8C). This finding is consistent with other related studies [16, 17], and may be due to decreased perfusion of adipose tissue and increased incidence of diabetes with or without insulin dependence. Furthermore, the relative increase in operative time in patients with high BMI suggests an increased open-chest exposure to the operating room environment that may contribute to the increased incidence of sternal wound infections.
The need for postoperative blood transfusions was systematically decreased with increasing BMI (Fig 7). Postbypass fluid retention similarly decreased as BMI increased. We believe these two findings are linked by the greater degree of hemodilution, or postbypass hematocrit (hemoglobin) observed in lower-BMI patients (Fig 4B). The CBP circuit prime volume is independent of patient size, and hence it will necessarily represent a greater fraction of the circulating blood-prime mixture during CPB in low-BMI than in high-BMI patients. A greater degree of hemodilution also means that the oncotic pressure gradient favors fluid extravasation. Such oncotic forces combine with the known effects of CPB on complement activation and the subsequent compromise of endothelial integrity to lead to increased net fluid retention through capillary leak [18–20].
Increased fluid retention after bypass increases the likelihood of postoperative lung edema with deleterious effects on lung mechanics and oxygenation and increased need for mechanical ventilatory support [18]. A further exacerbation in the lowest-BMI patients is their relative decrease in hemoglobin, which decreases oxygen reserve. These factors may explain the relatively increased ventilator dependence and consequently longer cardiovascular ICU stays in low-BMI patients (Figs 9B, 9C). Alternatively, the increased ventilator dependence in obese patients perhaps reflects impaired respiratory function due to relatively decreased vital capacity [18, 21] and sustained respiratory drive depression due to release of anesthetic agents stored in fatty tissues into the blood stream [21–23].
Overall and postoperative LOS were prolonged in low-BMI patients relative to all other patients, despite an increase in early in-hospital deaths, which tends to decrease LOS (Fig 9A). Conversely, however, this group also included a disproportionate number of outlier patients, whose excessively long hospitalizations increased the overall POLOS. Cardiovascular ICU LOS was prolonged in patients at both the low and high extremes of BMI; long cardiovascular ICU stays occurred in a larger fraction of the overall POLOS among the severely obese (Fig 9B). Expectedly, duration of hospitalization and relative stays in the cardiovascular ICU versus step-down unit directly affect cost of care.
The actual costs of CABG were lowest for patients who had near-normal BMIs; cost was comparatively increased in patients with the lowest and highest BMI values. Patients at extremes of body mass (and particularly those with low BMIs) were also more likely to endure excessively prolonged hospitalizations (LOS > 33 days) due to their complicated postoperative course. Interestingly, once these outlier patients (3%) were excluded, cost tended to increase in a linear fashion from low to high BMI. We believe that first, early postoperative deaths in patients with low BMIs, and second, relatively greater cardiovascular ICU stays in nonoutlier patients with very high BMIs are the primary reasons for this trend. Time spent in the operating room (OR) was typically longer in obese patients (Fig 5). That increased the hospital charges but had a minimal effect on true direct variable costs, because hospital OR charges per unit of time are arbitrary.
To allow for meaningful longer term comparisons, we compared relative survival at 2 years and 5 years after surgery (defined as intermediate and long-term survival rates, respectively), when patients were divided into four large patient subgroups, as defined above. Long-term follow-up on every nonoperative death in this study was done in February 2000 by searching the Social Security Administration Death Master File for an exact date of death (if it occurred). This analysis (see Fig 11) suggests that 5-year survival is similarly reduced in small and severely obese patients relative to those who are normal and mildly obese. Importantly, however, this similarity in long-term survival for severely obese and small patients undergoing CABG (60 ± 10 years and, 66 ± 10 years, respectively) occurs even though the former group was on average 6 years younger. These together point to two important conclusions about the role of obesity: First, that obesity in general (and severe obesity in particular) leads to earlier onset of surgical coronary artery disease and second, that severe obesity does not increase the risk of operative deaths, although the benefits of coronary revascularization are suboptimal in this group, compared with the benefits in those with normal BMI or mild obesity.
To explore the possible effects of disproportionate female representation at extremes of BMI (Fig 3B) on long-term survival in BMI subgroups, we analyzed the survival data for male (Fig 11B) and female (Fig 11C) patients separately. We also took into account that female patients were an average of 4 years older than male patients in all four BMI subgroups. These results indicate that 5-year survival trends were similar for the normal and mildly obese groups, regardless of gender. Furthermore, relative survival after 5 years for the BMI-based subgroups was also similar for male and female patients. In contrast, intermediate outcomes for low-BMI and very high–BMI patients tended to be different for male versus female patients. Specifically, severely obese males did not exhibit reduced survival compared to normal-BMI patients for the first 2 to 3 years after surgery (Fig 11B). Low-BMI male patients did not fair as well. After the third year, survival of male patients dropped more sharply and approached that of low-BMI males. Inexplicably, these intermediate term tendencies in small versus severely obese patient subgroups were essentially reversed in females (Figs 11B, 11C).
Our investigation into the role of body size in determining outcome of coronary revascularization suggests several conclusions. First, operative, economic and long-term outcomes were always optimal in CABG patients with BMI values at or around normal values ( BMI > 24 < to 30 kg/m2). Second, mild obesity ( BMI >30 to 34 kg/m2) does not appear to adversely affect any of these outcomes with the exception of slightly higher incidence of sternal wound infections. This relatively favorable outlook may however be due, at least partly, to these patients’ relatively younger age. Thirdly, in the immediate postoperative period, severely obese patients (BMI > 34 kg/m2) seemed to require prolonged ventilatory support and cardiovascular ICU stay. They also had an increased incidence of sternal wound infections. Those three factors combine to increase their cost of surgery. Yet operative death and other serious complications were not increased in those with severe obesity. The long-term benefits of coronary revascularization were, however, blunted in the severely obese as evidenced by a statistically significant reduction in their 5-year survival despite their relatively young age. Finally, the smallest patients (BMI 24 kg/m2), which included a disproportionate number of female patients, comprise the patient group with perhaps the worst outcome following CABG. In that group, operative mortality, postoperative stroke, myocardial infarction, and need for blood transfusions were all increased. Also, their intermediate (2-year) and long-term (5-year) survival was reduced significantly relative to those of normal patients. The apparent adverse effects of low BMI on long-term survival mostly reflect the subgroup’s older age and increased incidence of comorbid conditions (chronic obstructive pulmonary disease, congestive heart failure, left main coronary disease, and ejection fractions less than 30%). The worse immediate outcomes were more likely influenced by their small body size. Specifically, we believe that a greater hemodilutory effect of cardiopulmonary bypass plays an important role in such patients by: first, decreasing the oxygen carrying capacity leading to a greater need for blood transfusions, which have been recently shown to lead to worse operative outcomes [19]; second, leading to transvascular oncotic pressure gradients that favor extravasation and thus increased fluid retention by CPB-induced capillary leak; and third, increasing pulmonary fluid retention which compromises lung function necessitating longer postoperative mechanical ventilation. Whether these adverse effects of cardiopulmonary bypass in small patients also involve increased complement activation and release of other inflammatory mediators is not known; that is a subject that should be investigated in future studies. Importantly, however, these mediators have been shown to increase after transfusion in patients undergoing CABG [19, 20].
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