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Eur J Cardiothorac Surg 2003;23:368-373
© 2003 Elsevier Science NL

The effect of obesity on mid-term survival following coronary artery bypass surgery

Manoj Kuduvallia*, Antony D. Graysonb, Aung Y. Ooa, Brian M. Fabria, Abbas Rashida

a Department of Cardiothoracic Surgery,The Cardiothoracic Centre, Liverpool, UK
b Department of Research and Development, The Cardiothoracic Centre, Liverpool, UK

Received 18 September 2002; received in revised form 3 December 2002; accepted 8 December 2002.

* Corresponding author. Tel.: +44-0151-293-2412; fax: +44-0151-220-8573
e-mail: arashid{at}ccl-tr.nwest.nhs.uk


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Appendix A. Conference...
 References
 
Objective: Several studies have shown no significantly increased risk of in-hospital mortality for obese patients after coronary artery bypass grafting (CABG). However, the effect of obesity on mid-term survival has not been adequately studied. We set out to examine whether mid-term survival following CABG is affected by obesity. Methods: We performed a retrospective study of 4713 consecutive patients undergoing isolated CABG between April 1997 and September 2001. Body mass index (BMI) was used as the measure of obesity, with 3429 patients categorised as non-obese (BMI<30 kg/m2), and 1284 patients as obese (BMI>=30 kg/m2). Patient records were linked to the National Strategic Tracing Service, which records all deaths in the community, to establish current vital status. Deaths occurring over time were described using Kaplan–Meier techniques. To control for differences in patient characteristics, we used Cox proportional hazards analysis to calculate adjusted hazard ratios (HR) and 95% confidence intervals (CI). Results: Three hundred and thirty (7.0%) deaths occurred during the study period, with a mean follow-up of 2.4±1.4 years. The crude HR of mid-term mortality for obese patients was 1.09 (95% CI 0.86–1.39; P=0.457). After adjustment for core pre-operative factors, the adjusted HR of mid-term mortality for obese patients was 1.28 (95% CI 1.01–1.64; P=0.048). The adjusted freedom from death in the obese patients at 30 days, 1, 2, 3, and 4 years was 97.9, 95.9, 94.2, 92.4 and 90.5%, respectively, compared with 98.4, 96.8, 95.5, 94.0 and 92.5% for the non-obese patients. Conclusions: Although in-hospital mortality after CABG does not seem to be adversely affected by obesity there appears to be a significant increase in mortality in obese patients during a 4-year follow-up period.

Key Words: Obesity • Coronary artery bypass surgery • Mid-term survival • Risk adjustment


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 Appendix A. Conference...
 References
 
The proportion of obese patients undergoing coronary artery bypass graft (CABG) surgery in the United Kingdom is increasing [1]. Traditionally, obesity has been considered to be a significant risk factor for patients undergoing CABG [2,3]. However, there are various studies in the literature that have suggested that body size is not a risk factor for in-hospital mortality [4–10]. Some studies have also shown an increased risk of wound infections [4,5,9,11], atrial fibrillation [5,7,10] and respiratory complications [7,10,12] following CABG. Similar results were found in the in-hospital mortality and morbidity results of the patients in this study [13].

The impact of obesity on mid-term survival after CABG has not been fully described. The American college of cardiology/American heart association guidelines for coronary artery bypass surgery [3] have stated obesity to be a predictor of recurrence of angina, late myocardial infarction (MI) or any cardiac event. They however, do not state obesity as a predictor of poor long-term survival after CABG. Birkmeyer and colleagues, from the northern New England cardiovascular disease study group (NNECVDSG), have shown that morbid obesity was associated with significantly increased risks of mortality in both diabetic and non-diabetic patients [14]. The bypass angioplasty re-vascularisation investigation (BARI) has shown an increased risk in 5-year cardiac mortality as body mass index (BMI) increases [15]. A recent study also showed 5-year survival trends to be similarly worse for the smallest (BMI <24 kg/m2) and most severely obese patients (BMI >34 kg/m2) [16].

We analysed the effect of obesity on mid-term survival in patients undergoing isolated CABG at our institution, while adjusting for patient and disease characteristics.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 Appendix A. Conference...
 References
 
2.1. Patient population and data
We performed a retrospective study on a total of 4713 consecutive patients undergoing CABG surgery between 1st April 1997 and 30th September 2001 at the Cardiothoracic Centre, Liverpool. Patients undergoing CABG that was combined with a heart valve repair or replacement, resection of a ventricular aneurysm or other surgical procedures were not included.

Data was collected prospectively during the patient's admission as part of routine clinical practice on the following variables: age, sex, BMI, urgency of operation, prior cardiac surgery, New York heart association (NYHA) functional class, Canadian cardiovascular society (CCS) angina class, history of myocardial infarction, smoking, diabetes, hypercholesterolaemia, hypertension, peripheral vascular disease, cerebrovascular disease, respiratory disease, renal dysfunction, intravenous nitroglycerin therapy, cardiogenic shock, and intra-aortic balloon pump support as well as the extent of coronary disease, and left ventricular ejection fraction. Definitions and data collection methods have been previously published [17].

The patients' BMI were used as the measure of obesity. BMI, derived from Quetelet's formula, is calculated by dividing the weight in kilograms by the square of the height in metres [18,19]. BMI is a better indicator of obesity when compared to other indicators such as body surface area, because it corresponds least to the height of the patient and most to the actual amount of body fat as calculated by underwater weight measurements [19]. We classified anyone with a BMI >30 kg/m2 as obese, in line with the National Heart Lung and Blood Institute classification of obesity [20].

Different techniques of coronary re-vascularisation were used in our study. These included operations done with and without cardiopulmonary bypass (CPB). The technique of myocardial protection for patients done on CPB again varied according to operator preference. Although blood cardioplegia was the favoured choice, cold crystalloid cardioplegia and intermittent cross-clamp and fibrillation were also used by some surgeons.

2.2. Patient follow-up
Patient records were linked to the National Strategic Tracing Service (NSTS), which records all deaths in the United Kingdom. To establish current vital status, patients were matched to the NSTS based on patient name, National Health Service number, date of birth, gender, and postcode.

2.3. Statistical methods
Continuous variables are shown as median with 25th and 75th centiles and categorical variables are shown as a percentage with 95% confidence intervals (CI). Comparisons were made with Wilcoxon rank sum tests and Chi-square tests as appropriate. Deaths occurring as a function of time were described actuarially using the product limit methodology of Kaplan and Meier [21]. To control for differences in patient characteristics, we used Cox proportional hazards analysis to calculate adjusted hazard ratios (HR) and to risk adjust the Kaplan–Meier survival curves [22,23]. These variables included age, sex, previous cardiac surgery, left ventricular ejection fraction, left main stem stenosis, number of major coronary arteries with stenosis >70%, priority of surgery, peripheral vascular disease, diabetes, renal dysfunction, and respiratory disease [3]. In all cases a P value <0.05 was considered significant. All statistical analysis was performed with SAS for Windows Version 8.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 Appendix A. Conference...
 References
 
Overall, 3429 (72.7% (95% CI 71.5–74.0)) patients were classified as non-obese, while 1284 (27.3% (95% CI 25.9–28.5)) patients were classified as obese.

Table 1 lists patient and disease characteristics based on obesity category. There were no differences between patients' pre-operative characteristics according to severity of angina and dysponea, previous myocardial infarctions, current smokers, peripheral vascular disease, cerebrovascular disease, renal dysfunction, respiratory disease, left ventricular ejection fraction, number of diseased coronary vessels, cardiogenic shock, intra-aortic balloon pumps, prior cardiac surgery, and emergency surgery. Obese patients were, however, younger (P<0.001), less likely to require pre-operative intravenous nitroglycerin therapy (P=0.039), and less likely to have significant left main stem stenosis (P=0.028). Additionally, obese patients were more likely to be female (P<0.001), diabetic (P<0.001), hypertensive (P<0.001), and hypercholesterolaemic (P=0.001).


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  		Table 1. Patient and disease characteristicsa

 
Three hundred and thirty (7.0% (95% CI 6.3–7.8)) deaths occurred during the study with a total follow-up period of 11,303 patient-years (mean follow-up of 2.4 years). The number of patients at risk of death during the follow-up period for both study groups is shown in Table 2. Four-year mortality following CABG surgery was not significantly different between obese and non-obese patients (7.2% (95% CI 5.9–8.8) versus 6.9% (95% CI 6.1–7.8); P=0.692). The crude HR of mid-term mortality for obese patients was 1.09 (95% CI 0.86–1.39; P=0.457). Freedom from death in the obese patients at 30 days, 1, 2, 3, and 4 years was 97.3, 95.3, 93.8, 91.8 and 88.6%, respectively, compared with 97.8, 95.7, 93.9, 92.1 and 90.5% for the non-obese patients (Fig. 1 ).


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  		Table 2. Number of patients at risk during follow-up period

 


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  		Fig. 1. Observed survival following coronary artery bypass surgery.

 
After adjustment for baseline differences in patient and disease characteristics, the adjusted HR of mid-term mortality for obese patients was 1.28 (95% CI 1.01–1.64; P=0.048). The adjusted Kaplan–Meier survival curves are shown in Fig. 2 . The adjusted freedom from death in the obese patients at 30 days, 1, 2, 3, and 4 years was 97.9, 95.9, 94.2, 92.4 and 90.5%, respectively, compared with 98.4, 96.8, 95.5, 94.0 and 92.5% for the non-obese patients.



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  		Fig. 2. Adjusted survival following coronary artery bypass surgery, adjusted for age, sex, priority, previous surgery, ejection fraction, extent of disease, PVD, diabetes, renal dysfunction, and respiratory disease.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
Appendix A. Conference...
 References
 
Between 1960 and 1994, the overall percentage of obese people in the population has increased from 12.8 to 22.5%. The percentage of obese men has increased from 10.4 to 19.9%, and that of obese women has increased from 15.1 to 24.9%. [20].

Obesity is relatively common in Europe, especially among women and in southern and eastern European countries. Current prevalence data from individual national studies suggest that the range of obesity prevalence in European countries is from 10 to 20% for men, and 10–25% for women. Prevalence of obesity has increased by about 10–40% in the majority of European countries in the past 10 years. The most dramatic increase has been in the UK where it has more than doubled since 1980 [24].

Recent results of the National Health and Nutrition Examination Survey (NHANES) in the United States (1999) indicate that an estimated 61% of U.S. adults are either overweight or obese, defined as having a BMI of 25 kg/m2 or more. Among U.S. adults aged 20–74 years, obesity (defined as BMI greater than or equal to 30 kg/m2) has nearly doubled from approximately 15% in 1980 to an estimated 27% in 1999 (available from http://www.cdc.gov/nchs/products/pubs/pubd/hestats/obese/obse99.htm).

In the north west of England the number of obese patients (BMI >=30 kg/m2) undergoing isolated CABG has increased from 25.3% in the financial year of 1997/1998 to 30.6% in 2000/2001 (North west quality improvement programme in cardiac interventions. Cardiac surgery progress report: april 1997–march 2001 2nd edition. December 2001; available from http://www.nwheartaudit.nhs.uk/Progressreport1997-2001.pdf).

Several studies [4–6,16] including our own, have shown that obese patients are significantly younger. Therefore, it is increasingly important to study the survival of these obese patients after CABG.

In this study, as with other reports [4–6], obese (BMI >30 kg/m2) patients were more likely to be younger, female, diabetic and hypertensive. Additionally we observed that obese patients had a higher incidence of hypercholesterolaemia. This was also noted by Prasad et al. [7] and Koshal et al. [8]. Obese patients were also less likely to have significant left main stem stenosis. This finding was also seen in the study by Birkmeyer et al. [4]. In contrast, Prasad et al. [7] found an increased incidence of left main stem disease in the obese.

As with other reports [4,5,8,10,16], our study does not show a difference between obese and non-obese patients in early mortality. More details on this can be found in a published report, which examines the in-hospital outcomes for the patients in this study [13]. In brief, there was no association between obesity and in-hospital mortality, stroke, myocardial infarction, re-exploration for bleeding and renal failure in patients undergoing coronary artery bypass grafting. Obesity was significantly associated with atrial arrhythmia and sternal wound infections. The severely obese patients were more likely to develop harvest site infections and have prolonged mechanical ventilation and post-operative stays, compared to non-obese patients [13].

In this large, recent series of CABG patients, we have shown that obese patients have an increased risk of mortality over a 4-year follow up period. After multivariable adjustment for patient and disease characteristics, the 4-year post-CABG survival rate was 90.5% with obesity and 92.5% without, and the adjusted HR for mortality during the entire follow-up period was 1.28 (P=0.048). This is consistent with the findings of the NNECVDSG who found morbid obesity (BMI >=37 kg/m2) was associated with an increased risk of mortality, with an adjusted HR of 1.80 (P=0.025) [14]. Schwann et al. [16] showed that severely obese patients (BMI >34 kg/m2) had a significantly worse survival compared to non-obese patients. However, a multivariable analysis was not performed on their data, and therefore they did not identify other co-morbid conditions and their influence on poor long-term results in the obese patients. Gurm and colleagues [15] found that in CABG patients, there was a linear relationship between BMI and 5-year cardiac mortality (P<0.001). Adjusted relative risks of 5-year cardiac mortality according to levels of BMI were 0.0 (BMI <20 kg/m2), 1.0 (BMI 20–24.9 kg/m2), 2.02 (BMI 25–29.9 kg/m2), 3.16 (BMI 30–34.9 kg/m2), and 4.85 (BMI >=35 kg/m2).

Our study has a number of limitations. Firstly, it is an observational report and therefore could be confounded by selection bias. However, we have used Cox proportional hazards analysis to adjust for differences in patient and disease characteristics. The risk adjustment may not have taken into account variables that may affect the mid-term survival for our patients, but for this to have a dramatic effect on our conclusions, the variables used in the risk adjustment would have to be uncorrelated with the variables not adjusted for. For example, the impact of hypertension and hypercholesterolaemia on survival is diluted after adjusting for age, sex, priority, previous surgery, ejection fraction, extent of disease, PVD, diabetes, renal dysfunction, and respiratory disease. After adjusting for hypertension and hypercholesterolaemia, as well as the other variables mentioned above, survival is still significantly different between obese and non-obese patients (HR 1.28, P=0.049).

Another possible limitation is that we have treated obesity versus normal body size as a dichotomous variable, rather than treating body size as a continuous variable. This may increase the heterogeneity within the groups, with each group including a wide range of BMI. Obesity was treated as a dichotomous variable because we wanted to quantify the difference in mid-term survival between patients classified as obese, in line with recognised guidelines [20], and non-obese patients. Schwann and colleagues [16] found that small patients (BMI <24 kg/m2) had an increased risk of mortality during a 5-year follow-up, therefore the effect of obesity maybe underestimated in our study. We have also only looked at mid-term survival and did not take into account other outcomes such as the incidence of recurrent angina and quality of life. These outcomes will be of interest as our experience grows.

Rohs and colleagues examined the effect of CABG plus aggressive cardiac rehabilitation on the long-term prognosis of severely obese patients. They concluded that aggressive behavioural modification could help improve long-term function and survival of severely obese patients [25]. The impact of post-operative weight reduction in these patients is still not clearly defined. However, it would appear prudent to advise obese patients on the importance of weight reduction and change in life style to maximise the benefits of CABG.

In summary, although several studies have shown no in-hospital mortality differences between obese and non-obese patients, this study has highlighted a significant increase in mortality in obese patients during a 4-year follow-up period after CABG. Obesity may be a predictor of poor mid-term survival after coronary artery bypass surgery.


   Acknowledgments
 
We would like to acknowledge the co-operation given to us by all the consultant cardiac surgeons at the Cardiothoracic Centre, Liverpool: Mr J.A.C. Chalmers, Mr W.C. Dihmis, Mr M.J. Drakeley, Mr B.M.F, Miss E.M. Griffiths, Mr N. Mediratta, Mr R.D. Page, Mr D.M. Pullan, Mr A.R, and Mr W.I. Weir. We would also like to thank Janet Deane, who maintains the quality and ensures completeness of data collected in our cardiac surgery registry.


   Footnotes
 
Presented at the 16th Annual Meeting of the European Association for Cardio-thoracic Surgery, Monte Carlo, Monaco, September 22–25, 2002.


   Appendix A. Conference discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Appendix A. Conference...
References
 
Dr J. Roquette (Lisbon, Portugal): Did you already start that program of reducing weight?

Mr Kuduvalli: No. We have concluded this study recently. Hypercholesterolaemia and hypertension are actually quite aggressively controlled in the postoperative period by our cardiologists, but I think there is much more to be done in the program for postoperative rehabilitation and aggressive weight reduction. We find that most of the patients come back as outpatients in a few months time with an increase in weight rather than a decrease. I think there is room for more aggressive advice to these patients in this regard.

Dr Roquette: I didn't see if you had smoking.

Mr Kuduvalli: Yes, incidence of smoking was studied. There was no significant difference between the two groups.

Dr C. Miller (Houston, TX, USA): Did you look at very thin patients, did you look at the low end?

Mr Kuduvalli: No. As I said, we dealt with obesity and normal body mass index as a dichotomous variable, and this is probably one of the limitations of the study. But having the number of patients which we had in our database, we found that breaking them up into smaller groups actually diluted the statistical significance in the results. In the literature there is at least one study I know of which shows that there is a similar trend in patients with a body mass index less than 20, and they seem to have results as poor as the severe obese group.

Dr E. El-Ghafary (Cairo, Egypt): I would like just to inquire about why not to start the regimen of losing weight prior to the surgery in order to predict the patient? That is one.

The second thing is, what is the ideal way of losing weight, is that 5 kilo per month or 10 kilo, in order to protect those patients after the surgery?

Mr Kuduvalli: In answer to your first question, it does appear ideal to ask patients to reduce their weight prior to the operation. But in practicality this seems to be extremely difficult because they are quite limited in their exercise regimen because of their angina.

Secondly, there have been various studies, at least more than a half-a-dozen, to my knowledge, in the literature which have suggested that there is no increase in in-hospital mortality and some mild increases in in-hospital morbidity in these patients. So it seems to be a more practical suggestion to actually do their operation when they come to us and then start an aggressive program of rehabilitation and weight reduction in these patients.

In answer to your second question, there is not much in the literature to say exactly what is the ideal reduction in weight.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 Appendix A. Conference...
 References
 

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