Material and Method: Clinical and angiographic data from a total of 126 patients with a body mass index of ≥ 30 kg/m2 undergoing isolated coronary artery bypass grafting were included. Primary outcome of interest was postoperative occurrence of early low cardiac output syndrome. Angiographic score of each patient was calculated according to the method described by Gensini. Factors associated with primary outcome were evaluated using multivariate analysis.

Results: Low cardiac output syndrome occurred in 27 patients (21.4%). In multivariate analysis cross clamp time (OR: 1.064, 95% CI 1.026-1.103, p:0.001), age (OR: 1.099, 95% CI 1.028-1.175, p:0.006) and Gensini score (OR: 1.025, 95% CI 1.006-1.044, p:0.008) were found to be independent predictors of low cardiac output syndrome after coronary artery bypass grafting.

Conclusion: Overweight patients with higher Gensini angiographic scores more tend to have low cardiac output syndrome after CABG than those with lower scores. Protective effects of obesity against postoperative risks after coronary artery bypass grafting should be revisited.

Nevertheless, there has been a growing body of evidence suggesting a paradoxical relationship between obesity and survival in patients with cardiovascular disease, which has been so called ‘obesity paradox’ and defined as overweight and obese patients have better survival from cardiovascular diseases than those with normal weight. Although it is arguable that a high body-mass index is a well-surrogate of obesity, as it falls short distinguishing between high lean body mass and fat body mass ^4, obesity paradox in coronary heart disease has been well established depending not only on body-mass index evaluation but also on body fat or central obesity ⁵.

Obesity paradox has also gained popularity in the area of cardiac surgery. Several reports indicated the presence or absence of the paradox in patients undergoing coronary artery bypass grafting (CABG) ^6-9. Presence of obesity paradox in CAPB patients, which has been suggested as lower early mortality, shorter hospital stay after surgery and lower rates of complications, may partly be attributed to the fact that these patients are being referred to surgery at an earlier age despite carrying a higher risk profile. Also, besides complex metabolic and biologic features that potentially play important role in disease pathogenesis, cardiovascular mortality in obese patients was demonstrated to be influenced also by cardiorespiratory fitness ^10, which was also shown to affect morbidity and mortality after CABG ¹¹.

A number of diseased vessels were almost always taken into account as a potential risk factor in obese patients undergoing CABG, considering that extensive coronary artery involvement in an earlier age is likely to be a natural consequence of the metabolic derangement seen in obesity. However, the relationship is yet to be established since various studies showed conflicting results. Some authors showed that presence of triple vessel disease was significantly less common in higher vs lower body weight patients ^6,7, whereas the opposite was also shown ⁸. It was also suggested that there was no significant difference among patients with normal vs overweight in regard to number of vessels involved ⁹ or the relationship was totally ignored by some others ¹². Thus, whether extent of the coronary artery disease is truly associated with poor outcomes after CAGB has not yet been elucidated. We concluded a study on overweight patients undergoing isolated CABG, taking Gensini angiographic scores into account rather than number of vessels involved in order to better quantify the effect of disease extension on poor outcomes after surgery.

Patient demographics, counselling charts and laboratory results were recorded to reveal baseline characteristics of patients. Body-mass index values were based on measurements performed during spirometry assessment which is routinely being performed within a couple of days before the operation. Angiography views of the patients were obtained from the angiography database of the hospital and assessed by an independent cardiologist blinded to the outcome. Angiographic score of each patient was calculated according to the method described by Gensini ¹³.

Primary outcome of interest was postoperative occurrence and persistence (at least 4 hours) of early cardiac output syndrome which was defined as persistent hypotension, central venous pressure increase, low urine output and/or altered mental status. Secondary outcomes of interest were surgery related mortality and potential complications including, early myocardial infarction (a troponin level of ≥20 ng/ml in presence of hemodynamic derangement), sternal wound infection, drainage, respiratory distress, acute renal failure (sharp increase in creatinine level above 2.0 mg/dl), arrhythmia, prolonged intensive and hospital stay.

Sample size estimation:
A priori estimation was performed to find out the minimum sample size required to establish the relationship between higher angiographic scores and poor out-comes after CABG. We could not any study providing significant differences in mean Gensini scores between patients having or not having the outcome measure. However, in a recent study, Sinning et al ¹⁴ reported a cut-off value of 75.5 for Gensini score to predict worse outcomes including cardiovascular death and related outcomes. Therefore, we assumed that a ± 10% deviation from this cut-off value (67.95 vs. 83.05, with a standard deviation of 25.0 in each group) would probably produce clinically relevant outcomes (i.e. difference in Gensini scores between patients having or not having LCOS after CABG). Using the G-Power Statistical Software, setting a significance level of α:0.05 and power level of β:0.20, we found that a minimum of 118 patients were required for the present study. Search of the database was continued until slightly exceeding this level.

Statistical analysis:
Statistical analyses were performed using SPSS (Statistical Package for the Social Science) software. Continuous data following a normal distribution were expressed as mean and standard deviation, while those not following a normal distribution were expressed as median and ranges. Besides, categorical variables were reported as frequency and percentage. Independent sample T test for continuous data with a normal distribution, Mann Whitney U test for continuous data with non-normal distribution, Pearson Chi-Square test for categorical variables were performed for the group comparisons. In the analysis of predictive risk factor for adverse outcome, univariate predictors were determined with the univariate logistic regression analysis and an odds ratio was calculated for each parameter. Variables having a p value < 0.01 in the univariate analysis and non-correlated each other were included into the multivariate logistic regression analysis. Appropriateness of the model was tested using Akaike information criterion. P value ≤0.05 was considered to be statistically significant.

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Table 1: Baseline characteristics and operative data.

Table 2 shows postoperative outcomes. Low cardiac output syndrome occurred in 27 patients (21.4%). Among these, elevated lactate concentration (>2 mmol/L), elevated CVP (>10 cmH₂O), oliguria (<10 ml/h urine output) and dopamine infusion (3-5 μg/kg/min) were present in these patients whereas hypotension was present in 22 patients, altered mental status in 12 patients, catecholamine infusion in 16 patients. Placement of IABP was performed to 25 patients and counterpulsation was continued for at least 2 days.

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Table 2: Postoperative outcomes.

Overall mortality occurred in 7 patients, all of whom died due to LCOS; 2 patients died of early reperfusion injury and resultant hemodynamic derangement within 12 hours after the operation. In the remaining 5 patients death occurred within a range of 6 to 18 days and was due to various causes including; respiratory distress syndrome and ventilator associated pneumonia (3 patients), acute renal failure (1 patient), sepsis and multiorgan failure (1 patient). Overall, postoperative morbidities including respiratory distress, atrial fibrillation, acute renal failure (i.e. need for hemodialysis) and prolonged ICU stay were significantly more common in patients with LCOS than those without LCOS after CABG.

Parameters with a p value of less than 0.10 in univariate analysis were put into multivariate analysis (Table 3), except for retrograde cardioplegia was not included since it was found significantly correlated with both Gensini scores and cross clamp times. No other significant correlation was found among study parameters. In multivariate analysis, cross clamp time (OR: 1.064, 95% CI 1.026-1.103, p =0.001), age (OR: 1.099, 95% CI 1.028-1.175, p =0.006) and Gensini score (OR: 1.025, 95% CI 1.006-1.044, p =0.008) were found to be independent predictors of LCOS after CABG (Table 4).

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Table 3: Univariate analysis for the development of LCOS after CABG.

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Table 4: Multivariate analysis for the development of LCOS after CABG.

In line with a number of previous studies, postoperative mortality and morbidities were not too more common in this study but were close to mild risky population, roughly suggesting that obesity itself does not add too much risk for development of various complications after CABG. However, the number of our patients was limited to prove or disprove the presence of an obesity paradox since this term has been suggested upon researching on thousands of patients. Nevertheless, among the whole of overweight patients, some are supposed to be more likely to develop LCOS after surgery, which is often the case in all different populations undergoing CABG. Our retrospective observations provided that having higher angiographic severity scores might be the unique characteristics of such patients.

Why investigate whether there is a relationship between angiographic severity and CABG outcomes, whilst obesity paradox and its relevance have already been revealed in over weight population undergoing CABG? First, previous studies have fallen short in giving robust data establishing such paradox and been biased by several factors. In a recent study by Ardeshiri et al. ^15, authors reported that there was no significant difference between patients with a BMI lower or higher than 30 kg/m2 in regard to many CABG outcomes. However early outcomes such as cardiogenic shock, requirement of intraaortic balloon pump and myocardial infarction occurred in only a few patients in overweight group where total number of patients was 60. In another study on overweight patients undergoing CABG, Benedetto et al. ¹⁶ reported that obesity was not protective for late date after CABG although overweight status was not associated with increased risk of death early after the operation. Although this study results were based on 3821 obese patients initially, a propensity score analysis was performed to match two groups by confounders. Final analyses were performed n matched 203 patients. This approach is subject to criticism since an overmatch bias seems likely because patients with known risk factors that are almost unique to obese individuals in real life have totally been left outside the analysis. Producing a near-normal except high-weight population, this study fell short focusing the main problematic proportion of the overweight patients undergoing CABG operation. Stamou et al. ¹⁷ reporterd the presence of obesity paradox in their study on 2440 patients undergoing CABG (isolated and combined) but, in controversy, they did not perform any baseline matching between patients with or without high BMI. Patients in high weight and obesity groups were significantly younger and they significantly more tend to have diabetes and three vessel diseases, this time producing and important patient selection bias. Le-Bert et al. ⁸ sought to clarify the same issue on elderly obese patients under-going CABG and reported that obesity in elderly did not demonstrate an increased risk of postsurgical complications after CABG. In this study, intraaortic balloon pump was required in 45 (26.9%) vs 27 (28.7%) patients in normal vs overweight patients, respectively (p :0.95). These figures, being close to those we found in our study, indicates that one-fourth of patients with high BMI have low cardiac output syndrome after CABG, if they are not young enough to tolerate harmful effects of cardiopulmonary bypass on myocardium.

Second, and more important, is that metabolic obesity rather than anatomic obesity has recently increased in popularity since metabolically healthy subjects with high BMI have a lower prevalence of cardiac risk factors, suggesting a new definition for obesity that should be based on fat distribution rather than body mass index ¹⁸. Recently there have been many studies pointing out the importance of distinguishing metabolically healthy obese patients from those with abnormal metabolic status. Mørkedal et al. ¹⁹ reported that obesity without metabolic abnormalities does not increase the risk of acute myocardial infarction but there was significant increase in risk of heart failure. Supporting this, Hamer et al. ²⁰ reported that metabolically healthy obese individuals were not at increased risk of cardiovascular disease. On the contrary, Chang et al. ²¹ reported that patients with metabolically healthy obesity had a higher prevalence of subclinical atherosclerosis, indicating that obesity is harmful to coronary arteries regardless of its association with metabolic derangement. Nevertheless, the opposite of these findings was defended Rhee et al. ²². Importance of metabolically healthy status in overweight patients has thus still been controversial especially when cardiovascular disease prevalence or death was taken into consideration as the outcome parameters. Kwon et al. ²³ sought to clarify the relationship between metabolic obesity and angiographic coronary artery disease. Based on Korean national classification, they defined the metabolic obesity as presence of 3 or more of the following; larger waist circumference, elevated highdensity lipoprotein cholesterol and triglyceride level, high blood pressure and diabetes. Their findings were interesting; metabolically obese but normal weight individuals had higher severity in angiography than metabolically healthy normal weight individuals after adjustment for various risk factors and metabolically obese individuals had higher angiographic severity than non-metabolically obesity after adjustment for age and sex. This study particularly draws attention to the importance of distinguishing patients with more severe coronary artery disease extension from those having mild involvement of coronary arteries with atherosclerosis.

We think that our study provided some information regarding the identification of more risky ones among those patients with high BMI submitted to CABG. Since the correlation between angiographic severity and presence of some cardiovascular risk factors (coexistence has recently been called as metabolic obesity) has been well established ^24, it is not surprising to find out that angiographic severity may play an important role as an independent risk factor for development of LCOS after CABG.

Our study had several limitations. Retrospective design and lack of control group comprised of normal weight individuals was the major limitation. Use of certain criteria for determination of metabolic obesity and giving more detailed information which proportion our patients were indeed metabolically obese would have add much more information to the study. Finally, long term data could not to be provided because more than >50% patients could not respond to our invitation and also due to lack of adequate registry data regarding coronary artery disease outcomes.

In conclusion, we found that overweight patients with higher Gensini angiographic scores more tend to have low cardiac output syndrome after CABG than those with lower scores. Therefore, obesity paradox or in other words, protective effect of being overweight against adverse outcomes after CABG should be revisited in further study focusing on angiographic severity and its association with metabolic obesity since there seems to be an important cause and effect relationship between these two parameters.

Conflict of interest: None declared.

1) Ng M, Fleming T, Robinson M, et al. Global, regional and national prevalence of overweight and obesity in children and adults during 1980- 2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2014; 384: 766-81.

2) Lavie CJ, McAuley PA, Church TS, Milani RV, Blair SN. Obesity and cardiovascular diseases: implications regarding fitness, fatness, and severity in the obesity paradox. J Am Coll Cardiol 2014; 63: 1345-54.

3) Ghandehari H, Le V, Kamal-Bahl S, Bassin SL, Wong ND. Abdominal obesity and the spectrum of global cardiometabolic risks in US adults. Int J Obes 2009; 33: 239-48.

4) Bastien M, Poirier P, Lemieux I, Després JP. Overview of epidemiology and contribution of obesity to cardiovascular disease. Prog Cardiovasc Dis 2014; 56: 369-81.

5) De Schutter A, Lavie CJ, Milani RV. The impact of obesity on risk factors and prevalence of coronary heart disease: the obesity paradox. Prog Cardiovasc Dis 2014; 56: 401-8.

6) Reeves BC, Ascione R, Chamberlain MH, Angelini GD. Effect of body mass index onearly out-comes in patients undergoing coronary artery bypass surgery. J Am Coll Cardiol 2003; 42: 668-76.

7) Pan W, Hindler K, Lee VV, Vaughn WK, Collard CD. Obesity in diabetic patients undergoing coronary artery bypass graft surgery is associated with increased postoperative morbidity. Anesthesiology 2006; 104: 441-7.

8) Le-Bert G, Santana O, Pineda AM, Zamora C, Lamas GA, Lamelas J. The obesity paradox in elderly obese patients undergoing coronary artery bypass surgery. Interact Cardiovasc Thorac Surg 2011; 13: 124-7.

9) Kuduvalli M, Grayson AD, Oo AY, Fabri BM, Rashid A. Risk of morbidity and inhospital mortality in obese patients undergoing coronary artery bypass surgery. Eur J Cardiothorac Surg 2002; 22: 787-93.

10) McAuley PA, Artero EG, Sui X, et al. The obesity paradox, cardiorespiratory fitness and coronary heart disease. Mayo Clin Proc 2012; 87: 443-51.

11) Smith JL, Verrill TA, Boura JA, Sakwa MP, Shannon FL, Franklin BA. Effect of cardiorespiratory fitness on shortterm morbidity and mortality after coronary artery bypass grafting. Am J Cardiol 2013; 112: 1104-9.

12) Engel AM, McDonough S, Smith JM. Does an obese body mass index affect hospital outcomes after coronary artery bypass graft surgery? Ann Thorac Surg 2009; 88: 1793-800.

13) Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983; 51: 606.

14) Sinning C, Lillpopp L, Appelbaum S, Ojeda F, Zeller T, Schnabel R et al. Angiographic score assessment improves cardiovascular risk prediction: the clinical value of SYNTAX and Gensini application. Clin Res Cardiol 2013; 102: 495-503.

15) Ardeshiri M, Faritous Z, Ojaghi Haghighi Z, Hosseini S, Baghaei R. Effect of obesity on mortality and morbidity after coronary artery bypass grafting surgery in Iranian patients. Anesth Pain Med 2014; 4: 18884.

16) Benedetto U, Danese C, Codispoti M. Obesity paradox in coronary artery bypass grafting: myth or reality? J Thorac Cardiovasc Surg 2014; 147: 1517-23.

17) Stamou SC, Nussbaum M, Stiegel RM, Reames MK, Skipper ER, Robicsek F. Effect of body mass index on outcomes after cardiac surgery: is there an obesity paradox? Ann Thorac Surg 2011; 91: 42-7.

18) Iacobellis G, Sharma AM. Obesity and the heart: redefinition of the relationship. Obes Rev 2007; 8: 35-9.

19) Mørkedal B, Vatten LJ, Romundstad PR, Laugsand LE, Janszky I. Risk of myocardial infarction and heart failure among metabolically healthy but obese individuals: HUNT (Nord-Trøndelag Health Study), Norway. J Am Coll Cardiol 2014; 63: 1071-8.

20) Hamer M, Stamatakis E. Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. J Clin Endocrinol Metab 2012; 97: 2482-8.

21) Chang Y, Kim BK, Yun KE, et al. Metabolically-healthy obesity and coronary artery calcification. J Am Coll Cardiol 2014; 63: 2679-86.

22) Rhee EJ, Seo MH, Kim JD, et al. Metabolic health is more closely associated with coronary artery calcification than obesity. PLoS One 2013; 8: e74564.

23) Kwon BJ, Kim DW, Her SH, et al. Metabolically obese status with normal weight is associated with both the prevalence and severity of angiographic coronary artery disease. Metabolism 2013; 62: 952-60.

24) Sullivan DR, Marwick TH, Freedman SB. A new method of scoring coronary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors. Am Heart J 1990; 119: 1262-7.