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Ann Thorac Surg 2010;89:30-37. doi:10.1016/j.athoracsur.2009.09.050
© 2010 The Society of Thoracic Surgeons
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Original Articles: Adult Cardiac

Effect of Body Mass Index on Early and Late Mortality After Coronary Artery Bypass Grafting

Albert H.M. van Straten, MDa, Sander Bramer, MDa, Mohamed A. Soliman Hamad, MDa,*, André A.J. van Zundert, MD, PhDb,c, Elisabeth J. Martens, PhDd,e, Jacques P.A.M. Schönberger, MD, PhDa, Andre M. de Wolf, MDf

a Department of Cardiothoracic Surgery, Catharina Hospital, Eindhoven, the Netherlands
b Department of Anesthesiology, Catharina Hospital—Brabant Medical School, Eindhoven, the Netherlands
c University Hospital Ghent, Ghent, Belgium
d Department of Education and Research, Catharina Hospital, Eindhoven, the Netherlands
e Department of Medical Psychology, Center of Research on Psychology in Somatic Diseases, Tilburg University, Tilburg, the Netherlands
f Department of Anesthesiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois

Accepted for publication September 21, 2009.

Abbreviations and Acronyms BMI = body mass index; CABG = coronary artery bypass graft surgery; CI = confidence interval; COPD = chronic obstructive pulmonary disease; CrCl = creatinine clearance; EF = ejection fraction; HR = hazard ratio; OR = odds ratio; PVD = peripheral vascular disease

* Address correspondence to Dr Soliman Hamad, Department of Cardiothoracic Surgery, Catharina Hospital, Michelangelolaan 2, Postbus 1350, Eindhoven, 5602 ZA, the Netherlands (Email: aasmsn{at}cze.nl).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
Background: The effect of obesity on the long-term outcome after coronary artery bypass graft surgery (CABG) remains controversial. We analyzed data of patients undergoing CABG in a single center, to determine the predictive value of body mass index in combination with comorbidities on early and late mortality.

Methods: Early and late mortality of consecutive patients undergoing isolated CABG from January 1998 until December 2007 were determined. Patients were classified into five groups according to preoperative body mass index: underweight, normal weight, overweight, obese, and morbidly obese.

Results: After excluding 122 patients who were lost to follow-up and 236 patients with missing preoperative body mass index, 10,268 patients were studied. Multivariate logistic regression analyses showed that underweight was associated with higher early mortality (hazard ratio 2.63; 95% confidence interval: 1.13 to 6.11, p = 0.025). Multivariate Cox regression analyses did reveal morbid obesity as an independent predictor of late mortality (hazard ratio 1.67, 95% confidence interval: 1.15 to 2.43, p = 0.007).

Conclusions: Among patients undergoing isolated CABG, underweight is an independent predictor for early mortality, and morbid obesity is an independent predictor for late mortality.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
Obesity in the Western world has achieved alarming proportions and is related to morbidity such as diabetes mellitus, hypertension, and coronary artery disease, reduced life expectancy, impaired quality of life, and increased health care costs [1-4]. However, it remains controversial whether obesity is related to increased long-term mortality after coronary artery bypass graft surgery (CABG) [5-10]. In a recent meta-analysis, Oreopoulos and colleagues [11] showed that overweight and obesity are associated with a neutral or even beneficial effect on all-cause mortality after coronary revascularization. This controversial finding is described as the "obesity paradox." Because obesity is a potentially treatable condition, the identification of obesity as a risk factor for reduced life expectancy after CABG is an important issue.

The objective of this study was to determine the effect of body mass index (BMI) on early and late mortality after CABG.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
Patients
This study was performed after permission from the local Medical Ethics Committee. We analyzed data from patients undergoing isolated CABG in a single center in the Netherlands between January 1998 and December 2007. Clinical data, including demographics, risk factors, and complications, were prospectively collected in our database. We were not able to determine ethnicity in our patient groups, but the Dutch population is mostly Caucasian. Patients were placed into five groups based on BMI [9, 12–15]: underweight (BMI < 20 kg/m2), normal weight (BMI 20.0 to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2), obese (BMI 30.0 to 34.9 kg/m2), and morbidly obese (BMI > 34.9 kg/m2). Because most studies comparing BMI to early and late death after CABG used a limit of 20 kg/m2 for defining underweight, we decided not to use the cutoff point of 18.5 defined by the National Institution of Health [16].

Operative Techniques
All patients received short-acting anesthetic drugs to facilitate early extubation. Normothermic extracorporeal circulation used nonpulsatile flow. Cold crystalloid cardioplegia (St Thomas solution) or warm blood cardioplegia was used to induce and maintain cardioplegic arrest, according to the surgeon's preference. Patients undergoing CABG with extracorporeal circulation received low-dose aprotinin (2 million kallikrein inactivating units) during extracorporeal circulation, administered in the prime solution.

Follow-Up
Follow-up data concerning mortality were gathered using databases of health insurance companies. The data of 9% of the patient group could not initially be retrieved from these databases. We therefore contacted the patients' general practitioners or, if necessary, the authorities of the cities in which the patients lived at the time of the operation. In this way, we retrieved information about mortality for 99% of patients. Early mortality was defined as death within 30 days postoperatively or death at anytime if the patient did not leave the hospital or a transfer tertiary hospital alive; late mortality was defined as any-cause mortality more than 30 days postoperatively.

Statistical Analysis
Discrete variables were compared with the {chi}2 test and presented as numbers and percentages. Continuous variables were compared with the t test and analysis of variance and presented as mean ± SD. Univariate and multivariate logistic regression analyses were performed to investigate the impact of potential risk factors on early mortality. Cox proportional hazard regression analyses were performed to investigate the impact of potential risk factors on late mortality. Univariate analyses tested the potentially confounding effects of risk factors on mortality. If significant at p less than 0.05, confounders were included in the multivariable logistic and Cox regression analyses, in addition to the BMI groups (reference group: normal weight). Given the pronounced difference in sex distribution between the BMI groups, sex was included in the multivariate models as well. The cumulative long-term survival was estimated according to the Kaplan-Meier method, comparing differences between groups with the log-rank test. Survival was also estimated using the same method adjusted for other risk factors. The zero time point indicates the time of CABG. Odds ratios (OR) and hazard ratios (HR) with 95% confidence intervals (CI) are reported. A p value less than 0.05 was used for all tests to indicate statistical significance. All statistical analyses were performed using the SPSS statistical software (Statistical Product and Services Solutions, version 15.0; SPSS Inc, Chicago, IL).


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
During a 10-year period (January 1998 to December 2007), 10,626 patients underwent isolated CABG at our institution. After excluding 122 patients who were lost to follow-up and 236 patients with missing preoperative BMI, 10,268 patients were studied. Almost all patients who were lost to follow-up were foreigners or living abroad. Zero days were recorded for intraoperative deaths; minimum follow-up for surviving patients was 2 months. Mean follow-up was 65.5 ± 34.2 months (maximum follow-up was 123.6 months). Mean BMI of the study group was 27.1 ± 3.7 kg/m2 (range, 15.4 to 58.8 kg/m2). Distribution of BMI is shown in Figure 1. Baseline characteristics stratified by BMI groups are shown in Table 1. Morbidly obese patients were younger, and patients with underweight or morbid obesity were more often women than were normal weight, overweight, and obese patients. Diabetes mellitus and hypertension were associated with overweight, obesity, and morbid obesity. Patients who were underweight were more likely to have estimated left ventricular ejection fraction (EF) less than 35% and creatinine clearance (CrCl) less than 60 mL/min. Reexploration for any cause was more frequent in patients with underweight.


Figure 1
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  		Fig 1. Distribution of body mass index (BMI [kg/m2]) in 10,268 patients before coronary artery bypass graft surgery (CABG).

 

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  		Table 1 Baseline Characteristics of 10,268 Patients Stratified by Body Mass Index (BMI) Groups
 
Early and late mortality were higher among patients who were underweight compared with patients who were normal weight, overweight, obese, or morbidly obese, as shown in Table 2. Risk factors for early mortality identified by univariate and multivariate logistic regression analyses are shown in Table 3. Univariate logistic regression analyses revealed underweight as a risk factor for early mortality, whereas overweight, obesity, or morbid obesity were not. Other preoperative risk factors for early mortality identified by univariate analysis were advanced age, chronic obstructive pulmonary disease (COPD), diabetes, EF less than 35%, peripheral vascular disease (PVD), CrCl less than 60 mL/min, previous cardiac surgery, and emergency operation. Complications, such as perioperative myocardial infarction, reexploration, and perioperative need for intra-aortic balloon pump, were also identified by univariate analysis as risk factors for early mortality.


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  		Table 2 Early and Late Mortality Stratified by Preoperative Body Mass Index (BMI) Groups
 

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  		Table 3 Predictors of Early Mortality by Univariate and Multivariate Logistic Regression Analyses
 
Multivariate analysis revealed underweight as an independent risk factor for early mortality, along with advancing age, COPD, diabetes, EF less than 35%, CrCl less than 60 mL/min, previous cardiac surgery, and emergency operation.

Results of Cox regression analyses for late mortality are shown in Table 4. By univariate analysis, overweight was associated with lower late mortality. Other risk factors for late mortality by univariate analysis were advanced age, COPD, diabetes, EF less than 35%, CrCl less than 60 mL/min, PVD, hypertension, previous cardiac surgery, and CABG with the use of extracorporeal circulation. Complications such as perioperative myocardial infarction, perioperative need for intra-aortic balloon pump, and reexploration were also identified as risk factors for late mortality.


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  		Table 4 Predictors of Late Mortality by Univariate and Multivariate Cox Regression Analyses
 
Morbid obesity was significantly associated with late mortality by multivariate analysis entering only preoperative risk factors. Increasing age, COPD, diabetes, EF less than 35%, CrCl less than 60 mL/min, PVD, previous cardiac surgery, and male sex were independent risk factors as well.

In Figure 2, long-term survival stratified by BMI groups is depicted. Patients who were underweight had significantly lower survival compared with all other BMI groups (log-rank test, p = 0.02) Survival was lower for patients who were normal weight versus patients who were overweight (p = 0.001), whereas no other differences in long-term survival between BMI groups were significant (p > 0.05).


Figure 2
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  		Fig 2. Kaplan-Meier survival curves stratified by preoperative body mass index (BMI) group. Patients who were underweight had significantly lower survival compared with all other BMI groups (log-rank test, p = 0.02). Survival was lower among patients who were normal weight versus patients who were overweight (p = 0.001), whereas no other differences in long-term survival between BMI groups were significant (p > 0.05). (Cum = cumulative.)

 
Figure 3 shows the long-term survival of different patients groups adjusted for other significant risk factors that were identified by the multivariate regression analysis. These factors are age, COPD, diabetes, ejection fraction less than 35%, CrCl less than 60 mL/min, PVD, and male sex. Patients in both the underweight and the morbid obesity groups have lower long-term survival compared with the other groups (log-rank test, p = 0.03).


Figure 3
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  		Fig 3. Adjusted Kaplan-Meier survival curves stratified by preoperative body mass index (BMI) groups. Patients who were underweight or morbidly obese had significantly lower survival compared with all other BMI groups (log-rank test, p = 0.03). (Cum = cumulative.)

 

   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
This retrospective analysis of prospectively collected data demonstrates the predictive value of body weight extremes on mortality among patients undergoing CABG. Underweight is a predictor of early mortality, whereas morbid obesity is a predictor of late mortality. To be able to use BMI as a preoperative predictor of early and late mortality after CABG, the study design included only preoperative risk factors in the multivariate logistic regression model and the multivariate Cox regression model.

The predictive value of underweight for early mortality has been emphasized by other investigators. In a study by Engelman and colleagues [5], underweight patients (BMI less than 20 kg/m2) who underwent cardiac surgery had 10% mortality compared with 4% in the overall patient population. Reeves and colleagues [9] found operative mortality of 6.8% for underweight patients undergoing isolated CABG compared with less than 1% for patients with normal BMI. On the other hand, Rahmanian and colleagues [12] and Christakis and colleagues [14] did not find underweight patients at higher risk of hospital mortality compared with patients with BMI greater than 20 kg/m2. These conflicting results could be attributed to different preoperative patient profiles. In our series, underweight patients were more often women and more likely to have renal dysfunction (low CrCl), PVD, impaired left ventricular function (EF less than 35%), and COPD. Moreover, operative complications such as the need for intra-aortic balloon pump and reexploration occurred more often among underweight patients.

Several previous studies have shown increased postoperative morbidity among underweight patients [2, 5, 9], including low cardiac output syndrome, stroke, bleeding, and need for prolonged ventilation. Engelman and colleagues [5] showed a significant association between low BMI and reexploration for bleeding, a finding that we have shown as well. The explanation is that underweight patients experience relatively increased hemodilution caused by the priming volume of the heart-lung machine. That may exacerbate cardiopulmonary bypass–related coagulopathy, leading to increased postoperative bleeding in these patients.

All patients are screened for underlying diseases before undergoing CABG. If severe disease is present that might shorten life expectancy (for example, malignancy), therapies other than CABG, such as percutaneous coronary intervention, are considered. Therefore, severe life-shortening diseases that might cause underweight are unlikely to be present at the time of CABG. However, we cannot exclude the possibility of undetected underlying disease as a cause for both being underweight and early mortality. Further studies are needed to clarify this issue.

In accord with other several authors [2, 11, 17, 18], we observed no association between (nonmorbid) obesity and early and late mortality after CABG in our patients. In the study by Moulton and colleagues [19], obesity was a risk factor for sternal wound infection and atrial dysrhythmia but not for hospital mortality. Similar conclusions were reached by Birkmeyer and colleagues [20], who found that obesity was not associated with increased stroke or in-hospital mortality among patients undergoing CABG and that obesity was even associated with decreased risk of postoperative bleeding. Conversely, Gurm and colleagues [15] found that, among CABG-treated patients, each unit increase in BMI was associated with an 11% higher adjusted risk of 5-year cardiac mortality. The negative effect of morbid obesity on late morbidity confirms the results of others [9, 15].

We believe that proper long-term treatment of associated coronary risk factors is essential in improving the long-term survival of obese patients after CABG. The relatively high frequency of women and the relatively young age of the morbidly obese patients, with a presumably longer life expectancy, could have masked the negative effect of obesity on survival, as seen in some studies [11, 21]. Whether prevention and correction of body weight extremes may be helpful in preventing mortality after CABG remains to be investigated. Instead of the obesity paradox, the term "overweight paradox" seems more applicable in our population.

Female sex has been identified as an independent risk factor for early mortality after CABG surgery [22-25]. However, in this study, we did not confirm this finding. Male sex was a risk factor for late mortality.

Limitations of the Study
This study is a retrospective study. Therefore, we must be cautious in interpreting our results. Possible confounders, such as chronic illness and smoking, not studied could have biased the results. The use of arterial grafts was not entered in the analysis owing to the relatively small number of patients. Some perioperative complications—for example, prolonged ventilation, pulmonary complications, and wound infections—were not included in the analysis. These complications might also be correlated to obesity. The study endpoint was any-cause mortality. We were not able to report specific causes of death, morbidity, or hospital readmission that may have been equally interesting end points. The use of BMI as a risk factor does not differentiate between body fat and lean mass.

In conclusion, among patients undergoing isolated CABG, underweight was an independent predictor for early mortality, whereas morbid obesity was a significant predictor of late mortality.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

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