Abstract
OBJECTIVES
Obesity is associated with increased burden of cardiovascular risk factors, morbidity and mortality. However, several studies have counterintuitively shown better outcome after cardiac surgery in obese than in normal weight patients, a phenomenon known as obesity paradox. Furthermore, obesity has been linked with decreased need of red blood cell (RBC) transfusions. The purpose of this study was to evaluate the impact of body mass index (BMI) on 30-day mortality and RBC transfusions in patients undergoing cardiac surgery, a clinically important topic with conflicting previous data.
METHODS
We retrospectively investigated 1691 patients who underwent coronary and/or valve or aortic root surgery using cardiopulmonary bypass between 2013 and 2016. The patients were categorized by BMI based on the World Health Organization classification. For analysis, logistic regression was used with adjustment for potential confounding factors.
RESULTS
Of the patients, 28.7% were normal weight, 43.3% overweight, 20.5% mildly obese and 7.5% severely obese. Thirty-day mortality was 1.9% without significant differences between the BMI groups. 41.0% of patients received RBC transfusion. Overweight [odds ratio (OR) 0.75, 95% confidence interval (CI) 0.56–0.99, P = 0.045], mildly (OR 0.65, 95% CI 0.46–0.92, P = 0.016) and severely obese (OR 0.41, 95% CI 0.24–0.70, P = 0.001) patients needed less frequently RBC transfusions than patients with normal weight.
CONCLUSIONS
Obesity was not associated with 30-day mortality but was associated with lower use of RBC transfusions in cardiac surgery.
Keywords: Cardiac surgery, Body mass index, Obesity, Red blood cell transfusion, 30-day mortality
Obesity is a major health problem that increases the risk of cardiovascular diseases and shortens life expectancy [1, 2].
INTRODUCTION
Obesity is a major health problem that increases the risk of cardiovascular diseases and shortens life expectancy [1, 2]. However, in cardiac and non-cardiac surgery better outcome has been reported in overweight and obese than in normal weight patients, typically with a U-shaped association between body mass index (BMI) and mortality [3, 4]. This counterintuitive connection of obesity with equal or better outcomes of cardiac surgery, other cardiac interventions, non-cardiac surgery and several cardiovascular disease states has been designated as obesity paradox [5].
Obesity paradox has been reported in association with, e.g. acute coronary syndrome [6], acute myocardial infarction [7], heart failure [8], coronary artery disease [9], cardiac surgery [10–12] and non-cardiac surgery [13]. The explanations for the phenomenon are speculative, but bias and confounding factors have been proposed, as well as progressive catabolic state and lean mass loss opposed to metabolically healthy obesity [5]. Common potential confounding factors are smoking and pre-existing undiagnosed chronic disease, which both may result in low BMI and increased risk of death.
Red blood cell (RBC) transfusions have been shown to adversely affect the recovery and short- and long-term prognosis in patients undergoing cardiac surgery [14] and non-cardiac surgery [15]. Furthermore, RBC transfusions and BMI have been found to be associated with each other, with less transfusions in obese [16]. RBC transfusions have been associated not only with increased postoperative morbidity, such as renal dysfunction, wound infections and sepsis, but also with adverse influence on short- and long-term survival [16].
Considering the inconsistency of previous study results and the multifaceted associations between obesity and cardiac surgery outcome, our study aim was to evaluate the impact of BMI on 30-day mortality and RBC transfusions, and the association of RBC transfusions with 30-day mortality in patients undergoing open heart surgery.
PATIENTS AND METHODS
Ethics
The study was approved by the Research Ethics Committee of the Northern Savo Hospital District (approval no. 1694/13.02.00/2019, given on 18 December 2019). Informed consent was not required because the study was register based. The study complies with the Declaration of Helsinki.
Study design and patient population
The data was collected retrospectively from Kuopio University Hospital cardiac surgery database, which comprises 2559 consecutive adult patients undergoing cardiac surgery at Kuopio University Hospital from January 2013 to December 2016. Patients undergoing coronary artery bypass grafting (CABG), aortic valve replacement (AVR), AVR in combination with CABG, mitral valve repair (MVP) or mitral valve replacement (MVR), MVR/MVP in combination with CABG (MVP/MVR + CABG) and aortic root reconstruction using cardiopulmonary bypass were included in the study. Patients with other cardiac surgery (n = 349), off-pump surgery (n = 316) and incomplete data (n = 195) were excluded.
Definitions
BMI was calculated as weight (kg)/height2 (m2). Patients were divided into 4 subgroups based on the World Health Organization BMI classes: normal weight BMI 18.5–24.9, overweight BMI 25–29.9, obesity class I (mild obesity) BMI 30–34.9 and obesity classes II + III (moderate and morbid obesity) BMI ≥35 kg/m2. The obesity class II and obesity class III (BMI ≥40) groups were combined because of the low number of patients (n = 19) in the obesity class III group. For the same reason, the underweight (BMI <18.5 kg/m2) patients (n = 8) were excluded. The final study population consisted of 1691 patients.
Outcomes
The main outcomes of this study were 30-day all-cause mortality and the use of RBC transfusions. RBC transfusion trigger was a haemoglobin level <80 g/l during the perioperative period.
Data analysis and statistical methods
The normality of continuous variables was tested by Kolmogorov–Smirnov and Shapiro–Wilk methods. Continuous variables were not normally distributed. Consequently, they are presented as medians and interquartile ranges and categorical data as frequencies with percentages. Categorical variables were analysed with chi-squared test or Fisher’s exact test and continuous variables with Kruskal–Wallis test with post hoc pairwise comparisons. Logistic regression analysis was used to evaluate the association of BMI categories with 30-day mortality and RBC transfusions. The logistic regression analysis was adjusted at 4 levels (no adjustment, adjusted for age, adjusted for age and sex and fully adjusted). After studying the significance of relevant baseline covariates in a univariate model, the variables that were significant or close to significance (P < 0.10) were included in the fully adjusted model. The fully adjusted model included age, sex, type of surgery, New York Heart Association class, preoperative haemoglobin level, left ventricular ejection fraction, unstable angina pectoris, current or previous smoking, preoperative use of low molecular weight heparin and when analysing the association between RBC transfusions and 30-day mortality also the BMI classes as a categorized variable. To evaluate the robustness of the main result on the association between BMI classes and RBC transfusions a sensitivity analysis was performed by types of surgery using unadjusted logistic regression. Statistical analyses were performed with IBM SPSS Statistics 25.0 software for Windows (IBM Corp., Armonk, NY, USA). A P-value of < 0.05 was considered statistically significant.
RESULTS
Baseline characteristics
Out of the 1691 patients, 486 (28.7%) were normal weight (BMI 18.5–24.9 kg/m2), 733 (43.3%) overweight (BMI 25–29.9 kg/m2), 346 (20.5%) obese (BMI 30–34.9 kg/m2) and 126 (7.5%) severely obese (BMI ≥ 35 kg/m2). The majority of the patients were male (74.7%, n = 1264) and the mean age was 66.9 years (Table 1). Almost half of the patients (48.6%) underwent isolated CABG procedure. Patients with overweight or obesity underwent CABG more often than normal weight patients while mitral valve procedures were more common in the normal weight group (P < 0.001). Compared with the normal weight group, the overweight and obese patients were younger (P = 0.012) and had higher preoperative haemoglobin (P < 0.001), lower ejection fraction (P = 0.002) and higher New York Heart Association class (P = 0.021). They had more frequently unstable angina pectoris (P = 0.038) and use of low molecular weight heparin (P = 0.049) and they were more often current or previous smokers (P = 0.003).
Table 1:
Pre- and intraoperative clinical characteristics by body mass index groups
| Normal weight | Overweight | Obese class I | Obese class II–III | Overall | P-Value | |
|---|---|---|---|---|---|---|
| N = 486 | N = 733 | N = 346 | N = 126 | N = 1691 | ||
| Sex, male | 358 (73.7) | 585 (79.8) | 234 (67.6) | 87 (69.0) | 1264 (74.7) | <0.001 |
| Age (years) | 69 (60–76) | 68 (60–75) | 68 (61–75) | 65 (57–71) | 68 (60–75) | 0.002 |
| BMI (kg/m2) | 23.4 (22.1–24.2) | 27.3 (26.2–28.5) | 31.6 (30.8–32.9) | 36.9 (35.7–38.7) | 27.3 (24.6–30.4) | NA |
| eGFR (ml/min/1.73 m2) | 82.4 (70.6–92.6) | 79.9 (68.1–91.4) | 80.7 (64.8–80.8) | 81.8 (68.9–90.5) | 81.1 (67.6–91.3) | 0.220 |
| Haemoglobin (g/l) | 137 (126–147) | 141 (131–150) | 139 (128–149) | 143 (131–153) | 140 (128–149) | <0.001 |
| Smoking (current or previous) | 137 (29.6) | 256 (36.7) | 110 (33.2) | 56 (46.3) | 559 (34.7) | 0.003 |
| Current smoking | 69 (14.2) | 95 (13.0) | 37 (10.7) | 20 (15.9) | 221 (13.1) | 0.370 |
| LVEF (%) | 60 (50–65) | 60 (50–65) | 60 (50–63) | 55 (50–64) | 60 (50–65) | <0.001 |
| LVEF <40% | 32 (6.6) | 47 (6.5) | 26 (7.6) | 10 (7.9) | 115 (6.9) | 0.870 |
| History of atrial fibrillation | 44 (9.1) | 65 (8.9) | 34 (9.8) | 15 (9.5) | 158 (9.3) | 0.725 |
| History of stroke or TIA | 35 (7.2) | 55 (7.5) | 29 (8.4) | 8 (6.3) | 127 (7.5) | 0.876 |
| ASO | 40 (8.2) | 68 (9.3) | 32 (9.2) | 11 (8.7) | 151 (8.9) | 0.930 |
| Kidney disease | 31 (6.4) | 37 (5.0) | 19 (5.5) | 10 (7.9) | 97 (5.7) | 0.536 |
| COPD | 11 (2.3) | 25 (3.4) | 9 (2.6) | 1 (0.8) | 46 (2.7) | 0.322 |
| UAP | 86 (17.7) | 178 (24.3) | 69 (19.9) | 24 (19.0) | 357 (21.1) | 0.038 |
| NYHA | 0.021 | |||||
| No symptoms | 19 (3.9) | 27 (3.7) | 7 (2.0) | 6 (4.8) | 59 (3.5) | |
| 1 | 30 (6.2) | 42 (5.7) | 11 (3.2) | 8 (6.3) | 91 (5.4) | |
| 2 | 155 (31.9) | 212 (28.9) | 88 (25.4) | 33 (26.2) | 488 (28.9) | |
| 3 | 188 (38.7) | 283 (38.6) | 176 (50.9) | 56 (44.4) | 703 (41.6) | |
| 4 | 94 (19.3) | 169 (23.1) | 64 (18.5) | 23 (18.3) | 350 (20.7) | |
| Warfarin | 34 (7.0) | 55 (7.5) | 34 (9.8) | 11 (8.7) | 134 (7.9) | 0.461 |
| Clopidogrel | 8 (1.6) | 11 (1.5) | 4 (1.2) | 1 (0.8) | 24 (1.4) | 0.864 |
| LMWH | 65 (13.4) | 140 (19.1) | 58 (16.8) | 17 (13.5) | 280 (16.6) | 0.049 |
| Type of surgery | <0.001 | |||||
| Isolated CABG | 200 (41.2) | 394 (53.8) | 166 (48.0) | 62 (49.2) | 822 (48.6) | |
| AVR | 80 (16.5) | 103 (14.1) | 76 (22.0) | 24 (19.0) | 283 (16.7) | |
| AVR + CABG | 58 (11.9) | 79 (10.8) | 47 (13.6) | 16 (12.7) | 200 (11.8) | |
| MVP/MVR (+CABG) | 122 (25.1) | 112 (15.3) | 28 (8.1) | 13 (10.3) | 275 (16.3) | |
| AVR + ARR (+CABG) | 26 (5.3) | 45 (6.1) | 29 (8.4) | 11 (8.7) | 111 (6.6) |
Body mass index for weight categories: normal weight, 18.5–24.9; overweight, 25–29.9; obesity class I, 30–34.9; obesity class II–III, ≥35 kg/m2. The values are N (%) or median (interquartile range).
ARR: aortic root reconstruction; ASO: arteriosclerosis obliterans; AVR: aortic valve replacement; BMI: body mass index; CABG: coronary artery bypass grafting; COPD: chronic obstructive pulmonary disease; eGFR: estimated glomerular filtration rate; LMWH: low molecular weight heparin; LVEF: left ventricular ejection fraction; MVP: mitral valve repair; MVR: mitral valve replacement; NYHA: New York Heart Association class; TIA: transient ischaemic attack; UAP: unstable angina pectoris.
30-day mortality by body mass index categories
The overall 30-day mortality was 1.9%. It was similar across the BMI strata, at lowest (1.4%) in the normal weight group and at highest (2.6%) in the mildly obese group without a statistically significant difference (P = 0.639) (Table 2 and Fig. 1A). The unadjusted and adjusted odds ratios (ORs) for 30-day mortality were not significantly higher in the overweight and obese BMI groups than in the normal weight group (Table 3). The result remained in the fully adjusted model including type of surgery.
Table 2:
Peri- and postoperative characteristics across body mass index categories
| Normal weight | Overweight | Obese class I | Obese class II–III | Overall | P-Value | |
|---|---|---|---|---|---|---|
| n = 486 | n = 733 | n = 346 | n = 126 | n = 1691 | ||
| n 1 = 454 | n 1 = 686 | n 1 = 326 | n 1 = 117 | n 1 = 1583 | ||
| 30-day mortality | 7 (1.4) | 13 (1.8) | 9 (2.6) | 3 (2.4) | 32 (1.9) | 0.639 |
| Red blood cell transfusion (yes/no) | 222 (48.9) | 265 (38.6) | 128 (39.3) | 34 (29.1) | 649 (41.0) | <0.001 |
| Red blood cell transfusion | <0.001 | |||||
| 0 U | 232 (51.1) | 421 (61.4) | 198 (60.7) | 83 (70.9) | 934 (59.0) | |
| 1–2 U | 93 (20.5) | 122 (17.8) | 66 (20.2) | 12 (10.3) | 293 (18.5) | |
| 3–6 U | 101 (22.2) | 119 (17.3) | 49 (15.0) | 12 (10.3) | 281 (17.8) | |
| >6 U | 28 (6.2) | 24 (3.5) | 13 (4.0) | 10 (8.5) | 75 (4.7) | |
| Aortic cross-clamp time (min) | 88 (72–114) | 88 (68–112) | 89 (69–115) | 92 (74–110) | 89 (69–113) | 0.803 |
| Perfusion time (min) | 106 (84–137) | 104 (79–134) | 105 (81–138) | 106 (85–134) | 105 (82–136) | 0.709 |
n 1: the study population with red blood cell transfusion data. Body mass index for weight categories: normal weight, 18.5–24.9; overweight, 25–29.9; obesity class I, 30–34.9; obesity class II–III, ≥35 kg/m2. The values are n (%) or median (interquartile range).
Figure 1:
The association of 30-day mortality with body mass index categories (A), odds ratios for red blood cell transfusions by body mass index categories compared to the normal weight category (B) and 30-day mortality by red blood cell transfusion categories (C). In (B), the odds ratios are given with 4 levels of adjustments, the dashed line referring to the normal weight category with body mass index 18.5–24.9 kg/m2 as the reference. In (C), please note the logarithmic scale of Y-axis. Body mass index for weight categories: normal weight, 18.5–24.9; overweight, 25–29.9; obesity class I, 30–34.9; obesity class II–III, ≥35 kg/m2.
Table 3:
The odds ratios with 95% confidence intervals of overweight, obese class I and obese class II–III patients for 30-day mortality and red blood cell transfusions of ≥1 unit in comparison to normal weight patients
| 30-day mortality |
RBC transfusion |
|||
|---|---|---|---|---|
| Odds ratio (95% CI) | P-Value | Odds ratio (95% CI) | P-Value | |
| Overweight versus normal weight | ||||
| Unadjusted | 1.23 (0.49–3.12) | 0.654 | 0.66 (0.52–0.84) | <0.001 |
| Age adjusted | 1.27 (0.50–3.20) | 0.617 | 0.67 (0.52–0.85) | 0.001 |
| Age and sex adjusted | 1.31 (0.52–3.32) | 0.567 | 0.70 (0.54–0.91) | 0.007 |
| Fully adjusted | 1.74 (0.58–5.21) | 0.321 | 0.75 (0.56–0.99) | 0.045 |
| Obese class I versus normal weight | ||||
| Unadjusted | 1.83 (0.67–4.96) | 0.236 | 0.68 (0.51–0.90) | 0.008 |
| Age adjusted | 1.86 (0.69–5.06) | 0.222 | 0.67 (0.50–0.91) | 0.010 |
| Age and sex adjusted | 1.79 (0.66–4.88) | 0.253 | 0.61 (0.45–0.84) | 0.002 |
| Fully adjusted | 2.56 (0.79–8.30) | 0.118 | 0.65 (0.46–0.92) | 0.016 |
| Obese class II–III versus normal weight | ||||
| Unadjusted | 1.67 (0.43–6.55) | 0.463 | 0.43 (0.28–0.66) | <0.001 |
| Age adjusted | 1.90 (0.48–7.51) | 0.363 | 0.50 (0.32–0.78) | 0.002 |
| Age and sex adjusted | 1.77 (0.45–7.02) | 0.418 | 0.42 (0.26–0.68) | <0.001 |
| Fully adjusted | 1.74 (0.31–9.83) | 0.530 | 0.41 (0.24–0.70) | 0.001 |
Body mass index for weight categories: normal weight, 18.5–24.9; overweight, 25–29.9; obesity class I, 30–34.9; obesity class II–III, ≥35 kg/m2. The fully adjusted model includes age, sex, type of surgery, NYHA class, preoperative haemoglobin level, left ventricular ejection fraction, unstable angina pectoris, current or previous smoking, preoperative use of low molecular weight heparin.
CI: confidence interval; NYHA: New York Heart Association class; RBC: red blood cell.
Red blood cell transfusions by body mass index categories
A total of 694 (41.0%) patients received RBC transfusion (Table 2). There were significant differences across the BMI strata in the need of RBC transfusions (P < 0.001). The need of RBC transfusions was highest in the normal weight group (48.9%) and lowest in the severe and morbid obese group (29.1%) [OR 0.41, 95% confidence interval (CI) 0.24–0.70, P = 0.001] in comparison with the normal weight group (Table 3 and Fig. 1B). The need for RBC transfusions was between these 2 extremes in the 2 middle BMI categories: 38.6% (OR 0.75, 95% CI 0.56–0.99, P = 0.045) in overweight patients and 39.3% (OR 0.65, 95% CI 0.46–0.92, P = 0.016) in obese class I patients.
Sensitivity analysis by subgroups of type of surgery
The subgroup analysis by types of surgery showed that the association of RBC transfusions with BMI categories remained significant in CABG, AVR and AVR + CABG subgroups but was absent in mitral valve and aortic root operations (Fig. 2).
Figure 2:
Sensitivity analysis by subgroups of type of surgery. The odds ratios with 95% confidence intervals for the association of body mass index categories with red blood cell transfusions are shown in all patients and by surgery subtypes. (A) The odds ratios for red blood cell transfusions in overweight versus normal weight patients and (B) for red blood cell transfusions in obese versus normal weight patients. Body mass index for weight categories: normal weight, 18.5–24.9; overweight, 25–29.9; obesity, ≥30 kg/m2. ARR: aortic root reconstruction; AVR: aortic valve replacement; CABG: coronary artery bypass grafting; MVP: mitral valve repair; MVR: mitral valve replacement.
Association of red blood cell transfusions with 30-day mortality
Mortality at 30 days was significantly lower in patients who did not receive any RBC transfusion compared to those who did (0.3% vs 2.5%, P < 0.001) (Fig. 1C). The fully adjusted OR for 30-day mortality in transfused patients was 4.62 (95% CI 1.20–17.85, P = 0.027) in comparison with non-transfused patients. In this model, overweight, obesity class I and class II–III were not associated with 30-day mortality (P-values of 0.702, 0.411 and 0.933, respectively). When comparing patients receiving 0–2 units of RBC transfusions to patients receiving 3 or more units, the mortality rates were 0.5% and 4.2%, respectively, with P < 0.001 and fully adjusted OR of 5.33 (95% CI 1.80–15.81, P = 0.003). When comparing patients receiving >6 U to those receiving 1–2 U, the relative crude mortality was 12-fold (P < 0.001).
DISCUSSION
The main finding of our study was that overweight and obesity were not statistically significantly associated with 30-day mortality. The need of RBC transfusion was lower in overweight, mildly obese and severely obese patients than in patients with normal weight. RBC transfusion was associated with increased 30-day mortality.
There are several large studies including cardiac surgery patients showing equal or better short-term outcomes in obese than non-obese patients, and several extensive studies indicating better survival for overweight or mildly obese compared to normal weight patients. Potapov et al. [10] in their retrospective study of over 20 000 CABG patients found that patients with low BMI were at higher risk for postoperative complications than normal weight or even severely obese patients, while obesity was not a risk factor. However, BMI ≥36 kg/m2 was a hazard for postoperative infections. In another study including over 13 000 CABG patients comparing obese (BMI ≥30 kg/m2) and non-obese patients, obesity was not associated with increased postoperative in-hospital mortality but was associated with increased risk of respiratory failure, renal failure and surgical site infections, but at the same time with decreased risk of postoperative bleeding and reoperation due to bleeding [17]. As to the postoperative mortality, the result was similar as ours—obesity was not associated with increased 30-day mortality.
Johnson et al. reported a large study with over 78 000 patients undergoing CABG or CABG in combination with AVR and showed reverse J-shaped association between BMI and mortality. Overweight and obese patients had lower mortality and less adverse outcomes after cardiac surgery compared with normal weight, underweight and morbidly obese patients [12]. Mariscalco et al. [3] found in a cohort of 400 000 patients undergoing cardiac surgery that overweight and obese patients had lower in-hospital mortality than normal weight patients, while underweight patients had increased mortality. This paradoxical relationship between obesity and outcome remained unchanged when confounding factors and bias were carefully considered. Reeves et al. [18] reported based on a cohort of over 4 000 CABG patients that obesity did not increase 30-day mortality or other adverse outcomes, but underweight patients had a four-fold risk of 30-day mortality.
There are some studies reporting the association of BMI with mid- and long-term survival in cardiac surgery. Habib et al. found that the death hazard of the very obese (BMI ≥36 kg/m2) patients did not differ from normal weight patients during the first year but was clearly worse during years 1–6. Twelve-year survival was significantly worse for very small and very obese patients [19]. Similar results for 5-year survival were reported in a study of 3560 CABG patients, in which BMI ≤24 kg/m2 and BMI >34 kg/m2 were associated with worse survival trends [20].
Hartrumpf et al. [21] confirmed the presence of obesity paradox in a risk analysis of over 15 000 consecutive cardiac surgery patients divided into 4 BMI categories. The overweight category was a predictor of lower mortality. BMI was not considered as an independent risk predictor of early mortality. Instead of weight, they underlined the comorbidity burden of obese and, on the other hand, the frailty of underweight patients, suggesting cautious risk assessment and careful allocation to surgery.
In several studies, the mean BMI has been higher in the non-transfused patients compared to patients with transfusion [18, 22, 23]. According to the study by Reeves et al. [18], overweight, obese and severely obese heart surgery patients were less likely than normal weight patients to receive RBC transfusion. This finding is in line with our result, with less transfusions in overweight, obese and severely obese than normal weight patients, and moreover showing no difference in 30-day mortality between obese and normal weight patients. Furthermore, our sensitivity analysis showed that the result was consistent with the main result in case of AVR, CABG and combined AVR + CABG surgeries. This was not true for mitral valve surgery or aortic root reconstructions, where the risk of RBC transfusion was not lower in overweight or obese compared to normal weight patients. Kindo et al. [24] found in cardiac surgery patients under cardiopulmonary bypass that severe obesity with BMI ≥35 kg/m2 was a protective factor against excessive postoperative bleeding. An increase of 1 unit in BMI decreased the risk of RBC transfusion by 5% in CABG patients [16]. Overweight and obesity were independent predictors of less use of RBCs and lower 24-h chest-tube output [25].
Although the present study does not address the mechanisms of the inverse association between RBC transfusions and BMI, a multifactorial explanation seems plausible. Reduced hemodilution in obese, abundant mediastinal and abdominal fat leading to increased intrathoracic pressure and pressure on minor bleeding sites, and ‘prothrombotic paradox’ with higher levels of fibrinogen and less blood loss in severely obese patients could explain the inverse association between BMI and the need of RBC transfusions [24, 26].
Transfusion of RBCs has been associated with worse early and long-term survival, and each transfused RBC unit has been associated with a 77% increase in the risk of death, and the risk escalated rapidly after about 5 units [23]. Our study also showed an association between 30-day mortality and RBC transfusions. In order to assess the independent risk significance of non-massive blood transfusion, Surgenor et al. [27] minimized possible confounding factors bound to moderate and massive RBC transfusions by limiting the study to include only patients receiving no more than 1–2 U of RBCs compared to patients who received no RBC transfusion. A 16% higher long-term mortality risk after RBC transfusion of 1–2 U was observed. In a study including over 37 000 consecutive CABG patients, massive RBC transfusion was associated with a 6.4-fold increase in the risk of in-hospital death [28]. In our study, RBC transfusions >6 U were associated with a 12-fold crude risk of 30-day mortality compared to patients transfused with 1–2 U RBC.
Several mechanisms to explain the adverse effects of RBC transfusions have been proposed, such as transfusion-related immunomodulation, transfusion-associated circulatory overload, cellular hypoxia as delivery of oxygen to tissues may be limited due to depletion of 2,3-diphosphoglycerate in stored bank blood, transfusion-related acute lung injury and infections [16, 22]. RBC transfusion modulates inflammatory response to cardiac surgery by changing the levels of inflammatory mediators and augmenting the inflammatory response associated with cardiopulmonary bypass [29].
When examining the association of RBC transfusions with mortality in cardiac surgery, concomitant factors related both to RBC transfusions and premature death, such as preoperative anaemia, are important confounders. Based on data from >9000 cardiac surgery patients, preoperative anaemia was found to have a greater effect on 5-year mortality than RBC transfusions, when using a sophisticated statistical approach where multicollinearity was assessed applying variance influence factors [30]. In these data, higher BMI had a positive effect on survival [30].
To conclude, understanding the link between obesity and cardiac surgery outcome, obesity should not be the sole criteria for refraining from heart surgery. Based on our own data, RBC transfusions might at least partially account for obesity paradox in cardiac surgery, given the negative association between RBC transfusions and BMI. Although overweight and non-severe obesity were not associated with increased early mortality, other obesity-related complications after cardiac surgery should be carefully considered in clinical decision-making and perioperative patient care. A very uniform finding in literature is the association of severe obesity with early complications, especially with renal failure and deep sternal wound infections [3, 11, 26].
Limitations
We acknowledge some limitations. The links between BMI, RBC transfusions and the outcome of heart surgery are multifactorial and intertwined. Even though BMI classification is a simple and inexpensive way to categorize obesity, more detailed anthropometric measures and quantification of adipose tissue would provide additional information. Second, the retrospective nature of the study does set inherent limitations for the interpretation of the results. Data on RBC transfusion were missing in 6.8% of study participants, we did not have data on perioperative blood loss, need for resternotomy, or postoperative haemoglobin level and medium- and long-term mortality were not assessed. Moreover, this was a single-centre study and thus the results cannot be generalized to all cardiac surgery. Weight change before surgery, frailty, preoperative metabolic health and cardiorespiratory fitness were not evaluated.
CONCLUSION
BMI was not statistically significantly associated with 30-day mortality after cardiac surgery. The need of RBC transfusion was lower for overweight and obese patients in comparison to patients with normal weight. RBC transfusions were associated with an increase in 30-day mortality.
Conflict of interest: none declared.
Glossary
ABBREVIATIONS
- AVR
Aortic valve replacement
- BMI
Body mass index
- CABG
Coronary artery bypass grafting
- CI
Confidence interval
- MVP
Mitral valve repair
- MVR
Mitral valve replacement
- OR
Odds ratio
- RBC
Red blood cell
Contributor Information
Jenni Räsänen, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; Heart Center, Kuopio University Hospital, Kuopio, Finland.
Sten Ellam, Department of Anesthesiology and Operative Services, Kuopio University Hospital, Kuopio, Finland.
Juha Hartikainen, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; Heart Center, Kuopio University Hospital, Kuopio, Finland.
Auni Juutilainen, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
Jari Halonen, Institute of Clinical Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland; Heart Center, Kuopio University Hospital, Kuopio, Finland.
DATA AVAILABILITY
Data cannot be shared for ethical reasons.
Author contributions
Jenni Räsänen: Conceptualization; Formal analysis; Methodology; Writing—original draft; Writing—review & editing. Sten Ellam: Writing—review & editing. Juha Hartikainen: Conceptualization; Methodology; Supervision; Writing—review & editing. Auni Juutilainen: Conceptualization; Methodology; Supervision; Writing—review & editing. Jari Halonen: Conceptualization; Data curation; Methodology; Project administration; Supervision; Writing—review & editing.
Reviewer information
European Journal of Cardio-Thoracic Surgery thanks Takashi Kunihara, Alberto Guido Pozzoli, Nikolay O. Travin and the other anonymous reviewer(s) for their contribution to the peer review process of this article.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data cannot be shared for ethical reasons.