International Journal of Obesity (2014) 38, 1350–1356 © 2014 Macmillan Publishers Limited All rights reserved 0307-0565/14 www.nature.com/ijo
ORIGINAL ARTICLE
Impact of sleeve gastrectomy on red blood cell aggregation: a 12-month follow-up study M Wiewiora1, J Piecuch1, M Glück1, L Slowinska-Lozynska2 and K Sosada1 OBJECTIVE: To investigate the effects of weight loss due to laparoscopic sleeve gastrectomy (LSG) on erythrocyte aggregation and the relationship of anthropometric and plasmatic factors, such as plasma viscosity, fibrinogen and lipids, with erythrocyte aggregation. DESIGN AND SUBJECTS: The RBC aggregation and kinetics of the red blood cell aggregation were performed by the Laser-assisted Optical Rotational Cell Analyser (LORCA). Before the LSG and 6 and 12 months after the LSG, we evaluated the aggregation index (AI), amplitude (AMP) and aggregation half-time (t1/2), plasma viscosity, fibrinogen, glucose and lipids patterns in 15 non-diabetic obese subjects. RESULTS: The static and kinetic parameters of aggregation in obese patients at each time point after bariatric weight loss surgery were calculated and significant differences were observed at 12 months after surgery. AI and AMP decreased from 69.81 ± 5.12% and 27.43 ± 2.9 a.u. at baseline to 64.91 ± 5.94% and 22.15 ± 4.3 a.u. 12 months after surgery, respectively. The t1/2 increased from 1.7 (1.32–2.24) s at baseline compared with 2.02 (1.68–2.42) s at 12 months after the surgery. Plasma viscosity and fibrinogen decreased from 1.50 ± 0.093 mPa s and 3.0 ± 0.41 g l− 1 at baseline to 1.407 ± 0.062 mPa s and to 2.66 ± 0.25 g l − 1 12 months after surgery, respectively. AI correlated positively with BMI (r = 0.74, P = 0.001), waist circumference (r = 0.68, P = 0.005), fibrinogen (r = 0.52, P = 0.045) and plasma viscosity (r = 0.76, P = 0.001) and negatively with percentages of weight lost after surgery (r = − 0.54, P = 0.034). Multivariate analyses found that the BMI, fibrinogen and plasma viscosity independently influenced the AI. CONCLUSION: The study demonstrated that weight loss due to restrictive bariatric surgery can beneficially affect red cell aggregation parameters. The improvement of the RBC aggregation behaviours among obese subjects with weight loss due to LSG was associated with changes in plasmatic factors, especially fibrinogen. International Journal of Obesity (2014) 38, 1350–1356; doi:10.1038/ijo.2014.17 Keywords: red cell aggregation; sleeve gastrectomy; bariatric surgery
INTRODUCTION Obesity is associated with an increased risk of many medical problems, leading to increased morbidity1 and mortality.2 Studies have shown that disorders of some haemorheological parameters are correlated with comorbid pathologies associated with morbid obesity. Erythrocyte rheological changes have been observed in patients with cardiovascular diseases,3–5 hypertension6–8 and diabetes mellitus9–13 or metabolic syndrome.14 There is a recent literature showing that the obesity-associated increase in whole blood viscosity exhibits different profiles according to fat localisation.15,16 These data suggest that abdominal fat increases the blood viscosity due to haematocrit elevation, but overall adiposity is associated with increased plasma viscosity and red cell aggregation. However, other authors have shown the absence of improvement in abnormal erythrocyte rheology in obese women after short-term significant weight loss associated with a 10-day zero-calorie diet.17 Another recent study has not confirmed the correlation between blood rheology evaluated by the microchannel array flow analyser and BMI or WHR in male or female obese subjects.18 The author indicated that inflammation, oxidative stress and lifestyle habits are more important factors for the impairment of blood rheology than the degree of adiposity in obese individuals.
Haemorheological alterations in obesity have been reported by various groups, including disturbances of the rheological behaviour of blood, such as enhanced RBC aggregation. Erythrocyte hyperaggregation and a decrease in erythrocyte deformability have been well documented in obese patients.19–22 The impacts of a hypocaloric diet on the haemorheology of obese patients have been reported in a number of studies. Most of these studies showed that weight loss after dieting in obese patients contributed to normalising of the rheological profile with a corresponding improvement in the plasma viscosity, blood viscosity and red cell aggregation or deformability, depending on the size of weight loss.23–26 On the other hand, some studies have shown an absence of improvement in rheological parameters, including RBC aggregation, after weight loss associated with a low-calorie diet.27,16 Other authors have presented that a very low-calorie diet reduced erythrocyte aggregation at one month, but a prolonged low-calorie diet did not provide any additional benefit in weight or red cell aggregation, both of which returned to their basal values after 3 months of follow-up.29 Research on the impact of diet on haemorheology indicated a beneficial effect of weight loss on rheological profiles, as erythrocyte aggregation depends on the amount of weight lost and its long-term maintenance. The influence of bariatric surgery
1 Department of General and Bariatric Surgery and Emergency Medicine in Zabrze, Medical University of Silesia, Katowice, Poland and 2Chair and Department of Biophysics in Zabrze, Medical University of Silesia, Katowice, Poland. Correspondence: Dr M Wiewiora, Department of General and Bariatric Surgery and Emergency Medicine, Medical University of Silesia, ul. Sklodowskiej-Curie10, Zabrze 41-800, Poland. E-mail: [email protected] Received 20 October 2013; revised 6 January 2014; accepted 17 January 2014; accepted article preview online 31 January 2014; advance online publication, 25 February 2014
Red blood cell aggregations change after sleeve gastrectomy M Wiewiora et al
1351 on haemorheological parameters has been investigated in few studies up to now.30,31 To the best of our knowledge, the effects of sleeve gastrectomy on the rheological properties of blood in severely obese subjects have not yet been established. The aim of this study was to evaluate the effects of weight loss due to laparoscopic sleeve gastrectomy on erythrocyte aggregation at a 12-month follow-up. MATERIALS AND METHODS Patient characteristics We studied 17 morbidly obese patients who underwent sleeve gastrectomy. Of the 17 patients who were included in the study, 15 patients were finally analysed. Thrombophlebitis and pulmonary embolism occurred in one male, and one female had gynaecological disturbances requiring long-term hormonal therapy. Both these patients were excluded from subsequent postoperative comparisons. There were 5 males and 10 females in the study, with a mean age of 37.6 ± 7.12 years, mean weight of 141.77 ± 17.49 kg and a mean body mass index (BMI) of 49.0 ± 4.66 kg m −2. The factors used as exclusion criteria included those that could potentially influence the observed rheological blood parameters. Exclusion criteria included smoking, diabetes mellitus, thyroid disease, chronic kidney disease, anaemia and abnormal coagulation parameters, uncontrolled hypertension, history of leg vein thrombosis, antithrombotic or/and oestrogen or/and contraceptive therapy (o3 months before examination), hypolipemic treatment and lack of patient consent to participate. The exclusion criteria, which were related to the use of anticoagulants and antiplatelet agents, were applied to a period of 3 months before the study date. The study protocol was accepted by the ethical committee of the Medical University of Silesia, and all participants provided written consent. Patients enroled into the study underwent laparoscopic sleeve gastrectomy. In this study, laparoscopic sleeve gastrectomy was performed according to a commonly used technique.32 The greater curvature vessels were divided using the LigaSure device (Covidien, Mansfield, MA, USA). A longitudinal resection of the stomach was achieved using a linear cutting stapler (Echelon Flex 60 Endopath, Ethicon Endosurgery, Guaynabo, PR, USA), beginning from the point 5 to 6 cm proximal to the pylorus and continuing to the Angle of His and tightly abutting the bougie (a 36French), which had been placed transorally into the pyloric channel along the lesser curvature. Patients were followed for one year following the procedure. The patients were weighed, examined and interviewed by the surgeon preoperatively and at 1, 6 and 12 months after the operation. Blood was drawn for biochemical and rheological measurements preoperatively and at 6 and 12 months after the operation. Data from morbidly obese subjects were compared with those from control groups before surgery. The gender distribution and ages were similar in the obese and control groups. The control group consisted of 20 non-obese people without arterial hypertension, diabetes mellitus or any of the other above-listed features.
Haemorheological and biochemical measurements Blood samples were collected from the cubital vein with a syringe for biochemical examination and then anticoagulated with K3EDTA (1.5 mg ml− 1) for rheological tests.33 The rheological tests were performed at a stable temperature of 37 °C within two hours after the blood was collected. Plasma viscosity measurements were performed using a Brookfield DV-II+ (Wells-Brookfield, Brookfield Engineering Laboratories, Middleboro, MA, USA) cone-plate viscometer at shear rates of 900 s-1. The RBC aggregation and kinetics of the red blood cell aggregation were performed by the Laser-assisted Optical Rotational Cell Analyser—LORCA (Mechatronics, Zwaag, The Netherlands). The instrument and the methodological aspects have been described in detail elsewhere.34 The following parameters specific to the aggregation process were estimated: the aggregation index (AI in %), amplitude (in a.u.) and aggregation half-time (t1/2 in s), which express the kinetics of the aggregation process. Fibrinogen levels were measured using Clauss clotting method. The concentration of total cholesterol (T-CHOL), high-density lipoproteins (HDL), triglycerides (TG) and glucose levels were evaluated using an Integra 400 Plus Autoanalyzer (Roche Diagnostic, Mannheim, Germany). Low-density lipoproteins (LDL) were calculated using Friedewald formula. © 2014 Macmillan Publishers Limited
Statistical analysis Continuous variables are presented as the means ± s.d. or the median with the inter-quartile range, if not normally distributed. Categorical variables are presented as absolute numbers and percentages. The Shapiro–Wilk test was used for all continuous variables to test for their normal distribution. Differences between the morbidly obese and control groups before surgery were assessed using the unpaired Student’s t-test and the Mann–Whitney U-test for non-normally distributed data. Fisher’s exact test was performed to compare differences among the categorical data. Differences in each variable at the three time points (before surgery, 6 months and 12 months after surgery) were calculated by analysis of variance (ANOVA) tests, followed by Tukey’s post hoc or Friedman ANOVA tests and then Scheffe’s post hoc tests for non-normally distributed data. The paired Student’s t-test was performed to compare the differences of the data at 6 months and 12 months after surgery. The associations among continuous variables were tested using Pearson’s correlation or Spearman’s rank correlation. Independent predictors that influenced the aggregation index after surgery were determined by a multivariate regression model using the stepwise selection of anthropometric and biochemical parameters, with an entry criterion of P o0.05. Variables considered to be potential predictors for multivariate modelling were identified by univariate analyses and subsequently selected by stepwise backward selection. A P-value o0.05 was considered to be significant. This statistical analysis was performed using Statistica 10 (StatSoft Inc., Tulsa, OK, USA).
RESULTS The baseline characteristics of the study population and their comparisons with the control group are presented in Table 1. Anthropometric parameters decreased at each time point after surgery (Table 2). The percentages of excess weight lost at 6 months and 12 months after surgery were 46.19 ± 14.01 and 58.3 ± 21.77, respectively (P = 0.0048). The percentages of weight
Table 1. Baseline characteristics of obese patients and control participants Morbid obesity, N = 15 Gender Male Female
5 (33.3%) 10 (76.7%)
Age (years) Weight (kg) BMI (kg m −2) WHR AI (%) AMP (a.u.) t1/2 (s) Plasma viscosity (mPa s) Fibrinogen (g l− 1) SBP (mmHg) DBP (mmHg) FPG (mmol l − 1) T-CHOL (mg dl − 1) LDL (mg dl − 1) HDL (mg dl − 1) TG (mg dl − 1)
Control, N = 20 6 (30%) 14 (70%)
37.6 ± 7.12 36.7 ± 8.9 141.77 ± 17.49 68.32 ± 10.36 49.0 ± 4.66 23.7 ± 1.65 1.04 ± 0.12 0.83 ± 0.06 69.81 ± 5.12 56.43 ± 6.9 27.43 ± 2.9 23.41 ± 3.02 1.7 (1.32–2.24) 3.06 (2.15–3.78) 1.50 ± 0.093 1.37 ± 0.08 3.0 ± 0.41 2.33 ± 0.39 140 (135–140) 120 (110–130) 90 (80–90) 75 (70–80) 5.31 ± 0.66 4.63 ± 0.57 195.66 ± 37.94 200.36 ± 39.4 123.66 ± 32.82 124.82 ± 36.15 43.9 ± 11.74 67.84 ± 15.8 145 (120–167) 68 (54–100)
P-value
0.574 0.571 0.803 o0.0001 o0.0001 o0.0001 o0.0001 0.00038 0.00011 0.00012 o0.0001 0.00010 0.01490 0.00262 0.762 0.921 o0.0001 o0.0001
Abbreviations: AI, aggregation index; AMP, amplitude; a.u., arbitrary units; BMI, body mass index; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HDL, high-density lipoproteins cholesterol; LDL, low-density lipoproteins cholesterol; SBP, systolic blood pressure; t1/2, aggregation half-time; T-CHOL, total cholesterol; TG, triglycerides; WHR, waist-to-hip circumference ratio. Data are presented as the means ± s.d. or median (inter-quartile range) for continuous variables or as prevalences for categorical data. Group differences were calculated using the unpaired Student’s t-test or the Mann–Whitney U-test for non-normally distributed data and the Fisher’s exact test for categorical data.
International Journal of Obesity (2014) 1350 – 1356
Red blood cell aggregations change after sleeve gastrectomy M Wiewiora et al
1352 Table 2.
Differences in each variable before surgery and at each time point after surgery Baseline, N = 15
Weight (kg) BMI (kg m −2) Waist circumference (cm) Hip circumference (cm) WHR AI (%) AMP (a.u.) t1/2 (s) Plasma viscosity (mPa s) Fibrinogen (g l − 1) SBP (mmHg) DBP (mmHg) FPG (mmol l − 1) T-CHOL (mg dl − 1) LDL (mg dl − 1) HDL (mg dl − 1) TG (mg dl − 1)
141.77 ± 17.49 49.0 ± 4.66 136.93 ± 12.98 131.8 ± 13.02 1.04 ± 0.12 69.81 ± 5.12 27.43 ± 2.9 1.7 (1.32–2.24) 1.50 ± 0.093 3.0 ± 0.41 140 (135–140) 90 (80–90) 5.31 ± 0.66 195.66 ± 37.94 123.66 ± 32.82 43.9 ± 11.74 145 (120–167)
6 Months, N = 15
105.0 ± 8.79 36.69 ± 3.98 109.76 ± 12.3 125.53 ± 16.18 0.88 ± 0.12 65.78 ± 5.18 23.91 ± 4.5 1.72 (1.64–1.98) 1.480 ± 0.104 3.11 ± 0.33 130 (120–140) 80 (80–90) 5.21 ± 0.45 184.5 ± 46.74 110.32 ± 34.3 50.92 ± 13.15 96 (81.5–137)
12 Months, N = 15
98.93 ± 8.45 34.47 ± 4.19 108.7 ± 10.96 124.53 ± 10.86 0.87 ± 0.08 64.91 ± 5.94 22.15 ± 4.3 2.02 (1.68–2.42) 1.407 ± 0.062 2.66 ± 0.25 120 (110–140) 80 (80–90) 5.04 ± 0.39 200.53 ± 48.85 119.86 ± 39.22 58.47 ± 13.71 101 (68–164)
P-value 6 Months vs baseline
12 Months vs baseline
0.000131 0.000122 0.000123 0.440623 0.001632 0.138123 0.083863 0.777736 0.819185 0.668237 0.091627 0.978274 0.869696 0.795638 0.626328 0.346560 0.108313
0.000122 0.000122 0.000122 0.308368 0.000971 0.046991 0.003938 0.09336 0.016324 0.029582 0.003734 0.981613 0.344446 0.952138 0.962575 0.009930 0.167612
Abbreviations: AI, aggregation index; AMP, amplitude; a.u., arbitrary units; BMI, body mass index; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HDL, high-density lipoproteins cholesterol; LDL, low-density lipoproteins cholesterol; SBP, systolic blood pressure; t1/2, aggregation half-time; T-CHOL, total cholesterol; TG, triglycerides; WHR, waist-to-hip circumference ratio. Data are the means ± s.d. or medians (inter-quartile range) for continuous variables. Group differences at the three time points (before surgery, 6 months and 12 months after surgery) were calculated by the analysis of variance.
lost also significantly changed at each time point after sleeve gastrectomy, with 23.76 ± 6.99 and 29.39 ± 9.47 at 6 months and 12 months after surgery, respectively (P = 0.0091). The haemorheological parameters also changed postoperatively at each time point (Table 2). Significant differences were observed for AI, which decreased from 69.81 ± 5.12% at baseline compared with 64.91 ± 5.94% at 12 months after surgery (P = 0.046) and for amplitude, which decreased from 27.43 ± 2.9 a.u. at baseline to 22.15 ± 4.3 a.u. at 12 months after surgery (P = 0.0039). Similar decreasing trends were observed for plasma viscosity and fibrinogen concentration. Plasma viscosity significantly decreased from 1.50 ± 0.093 mPa s at baseline to 1.407 ± 0.062 mPa s at 12 months after surgery (P = 0.016). Fibrinogen significantly decreased from 3.0 ± 0.41 g l − 1 at baseline to 2.66 ± 0.25 g l − 1 at 12 months after surgery (P = 0.029). The t1/2 tended to be higher at baseline compared with 12 months after surgery, from 1.7 (1.32–2.24) s to 2.02 (1.68–2.42) s (P = 0.09). Changes in the lipid patterns at each time point before and after surgery were not significant, except for HDL (Table 2). The HDL increased from 43.9 ± 11.74 mg dl − 1 at baseline to 58.47 ± 13.71 mg dl − 1 at 12 months after surgery (P = 0.009). The correlation between AI and the anthropometric parameters is presented in Figure 1. AI correlated positively with BMI (r = 0.7470, P = 0.001) and waist circumference (r = 0.6812, P = 0.005) and negatively with %WL (r = − 0.5490, P = 0.034). The correlation between AI and fibrinogen (r = 0.5236, P = 0.045), T-CHOL (r = 0.5555, P = 0.032) and plasma viscosity (r = 0.7613, P = 0.001) is presented in Figure 2. Univariate analyses revealed six potential predictors influencing the AI and the t1/2. These predictors included the BMI, %WL, waist circumference, fibrinogen, T-CHOL and plasma viscosity (Tables 3 and 4). Multivariate analyses found BMI (β = 0.7477, P = 0.0427; Table 3), fibrinogen (β = 0.3938, P = 0.0294; Table 4) and plasma viscosity (β = 0.4739, P = 0.0213; Table 4) to be variables that independently influenced the AI. DISCUSSION Haemorheological disturbances may determine the quality of the blood flow in both the microcirculation network and in macrocirculation, especially in obese individuals.35–38 It has been clearly International Journal of Obesity (2014) 1350 – 1356
shown that RBC aggregation has an important role in determining the low shear blood viscosity39 and contributes to blood flow.40,41 Generally, increasing blood viscosity with increasing RBC aggregates forms rouleaux structures with larger geometries at low shear rates. Studies have shown that RBC aggregation promotes the axial accumulation of RBCs in ex vivo investigations into the tube flow42 and microcirculation of animal models,43,44 resulting in a two-phase flow consisting of a core of aggregates and a cell-free layer. The ability of RBCs to aggregate into the slow-moving plasma layer is most important in determining the effects of this hydrodynamic resistance at low flow rates in tubes42 and capillaries,45 as the dimension of this effect increases with red cell hyperaggregation. Other authors have indicated that red blood cell aggregation may alter the cell-free layer variability, especially at low shear rates.46,47 The effect of RBC aggregation on tissue blood flow is not one-sided, as the haemodynamic consequences of RBC aggregation can affect the amount of tissue perfusion resulting from several interrelated mechanisms. These mechanisms include the axial accumulation of RBC, viscosity and resistance in the cell-free layer and the haematocrit of the microvessels or wall shear stress, both of which depend on the behaviour of the RBC aggregates. Axial accumulation is also the primary mechanism underlying the Fahraeus–Lindqvist effect, which refers to the decrease in the viscosity of blood with decreasing vessel radius, as observed in vessels less than 500 μm in diameter. Plasma skimming and the Fahraeus effect both contribute to the significantly lower microvascular haematocrit compared with arterial or venous haematocrit. This reduced microvessel haematocrit contributes to a lower than expected haemodynamic resistance. Thus, the effect of enhanced red blood cell aggregation on microcirculatory blood flow is biphasic and some degree of increased RBC aggregation does not always induce significant microcirculatory blood flow disturbances. The hyperaggregation of RBCs result in a decreased tissue blood perfusion and may also increase the risk of thrombosis.48 These results confirmed that obesity is associated with alterations in RBC rheology, expressed by an increased extent of total aggregation and the spontaneous ability to aggregate. Alterations in the kinetics of RBC aggregation expressed by shortening t1/2 indicate that RBCs in obese individuals form aggregates and rouleaux © 2014 Macmillan Publishers Limited
Red blood cell aggregations change after sleeve gastrectomy M Wiewiora et al
1353
Figure 1. Correlation between AI and anthropometric parameters: (a) with BMI; (b) with waist circumference and (c) with %WL. The associations among the variables were tested using Pearson’s correlations.
Figure 2. Correlation between AI and biochemical parameters: (a) with fibrinogen; (b) with T-CHOL and (c) with plasma viscosity. The associations among the variables were tested using Pearson’s correlations.
within a shorter time after their disaggregation than in normalweight individuals.34 A recent literature review concerning the relationships among body composition, blood rheology and exercise performance showed that red cell aggregation is correlated to fat mass not only in obese or overweight individuals but also within a physiological range of fat mass.49 Observations of rugby players may suggest that this proportionality between fat mass and erythrocyte aggregability is not an essentially pathologic mechanism but a physiological relationship.49,50 Other authors
have shown that the obesity-associated increase in whole blood viscosity occurs through different mechanisms on the basis of fat localisation.15 The authors speculated that changes in blood rheology, such as moderate increases in RBC aggregation and deformability or plasma viscosity related to some degree of increased fat mass are physiological consequences of sedentarity and may be an adaptive mechanism beneficial for circulation. However, at a critical capillary radius, the increase in the blood viscosity depends on the rigidity of the blood cells,
© 2014 Macmillan Publishers Limited
International Journal of Obesity (2014) 1350 – 1356
Red blood cell aggregations change after sleeve gastrectomy M Wiewiora et al
1354 Table 3.
Regression analysis of the potential anthropometric predictors of influences on the aggregation parameters at 12 months after sleeve gastrectomy Variable
Univariate regression β
SEβ
P-value
0.7894 −0.5489 −0.3962 0.6811 0.1635 0.4919
0.17
0.00046 0.0340 0.143 0.00517 0.560 0.0624
AI BMI %WL %EWL Waist circumference Hip circumference WHR
Multivariate regression
0.25 0.2 0.27 0.24
BMI % WL Waist circumference
β
SEβ
P-value
R2
0.7477 0.1646 0.2181
0.3 0.28 0.28
0.0427 0.5694 0.4569
0.55
Abbreviations: BMI, body mass index; EWL, excess weight lost; R2, coefficient of determination; SEβ, standard error of β; WL, weight lost; WHR, waist-to-hip circumference ratio. P-values o0.05 are shown in bold.
Table 4.
Regression analysis of the potential biochemical predictors of influences on the aggregation index (AI) at 12 months after sleeve gastrectomy Variable
SBP DBP Fibrinogen FPG T-CHOL LDL HDL TG Plasma viscosity
Univariate regression
Multivariate regression
β
SEβ
P-value
0.3751 0.4058 0.5236 0.1591 0.5554 0.4402 0.3340 0.3038 0.7612
0.27 0.27 0.23 0.27 0.23 0.24 0.26 0.26 0.17
0.206 0.168 0.0451 0.570 0.0315 0.10 0.223 0.27 0.0009
Fibrinogen T-CHOL Plasma viscosity
β
SEβ
P-value
R2
0.3938 0.3599 0.4739
0.15 0.16 0.17
0.0294 0.0553 0.0213
0.703
Abbreviations: DBP, diastolic blood pressure; FPG, fasting plasma glucose; HDL, high-density lipoproteins cholesterol; LDL, low-density lipoproteins cholesterol; R2, coefficient of determination; SBP, systolic blood pressure; SEβ, standard error of β; T-CHOL, total cholesterol; TG, triglycerides. P-values o 0.05 are shown in bold.
RBC aggregation and other rheological properties of the blood.51 If rheological disorders have reached critical levels, resistance to flow may increase. In this study, we demonstrated that weight loss owing to restrictive bariatric surgery affects red cell aggregation parameters. We found changes in the static and kinetic parameters of aggregation in obese patients at each time point after bariatric weight loss surgery, but significant differences were only observed at 12 months after surgery. We observed a decrease in extent of aggregation and an elevated aggregation half-time, which indicate that spontaneous ability to aggregate was reduced, compared with baseline values. These findings also suggest that the beneficial effects of restrictive bariatric surgery on the hyperaggregation of RBCs are associated with obesity, depending on the size of the weight loss in the postoperative period. Most studies that were concerned with the influence of a hypocaloric diet on RBC aggregation in obese patients reported that weight loss after dieting in obese patients normalised the aggregation of the RBCs, effecting a corresponding improvement in the erythrocyte aggregation index.24–26 Other authors have shown the absence of improvement in rheological parameters, including RBC aggregation, after weight loss associated with a low-calorie diet.27,28 Sola et al.29 showed that a very low-calorie diet of 458 kcal per day reduced erythrocyte aggregation at one month, but a prolonged low-calorie diet providing 1500 kcal per day did not provide any additional benefit for red cell aggregation, which returned to its basal value at 3 months follow-up. Weight loss surgery is able to induce a long-term normalisation of RBC aggregation in obese subjects because it is more effective in weight control than various diets. To our knowledge, the influence International Journal of Obesity (2014) 1350 – 1356
of bariatric surgery on haemorheological parameters has been investigated in two previous papers. In these previous papers, vertical-banded gastroplasty was shown to induce some beneficial changes in the level of RBC aggregation.30 In a recent study, Capuano et al.31 observed a similarly beneficial effect of weight loss due restrictive bariatric procedures. The authors found a reduction in the AI and a slight increase in the t1/2 of obese subjects 6 months after adjustable gastric banding, but they did not analyse the impact of the evaluated anthropometric and biochemical parameters on erythrocyte aggregation. We found similar changes specific to the RBC aggregation process parameters at 12 months after sleeve gastrectomy. This might be explained by the fact that, in the study performed by Capuano et al., obese subjects underwent gastric restrictive bariatric surgery followed by a programme of lifestyle changes, including education on a Mediterranean diet and daily moderate exercise. We found not only a significant improvement in the rheological parameters but also an improved plasma viscosity and fibrinogen level at 12 months after surgery. It has been found that obesity is associated with plasma hyperviscosity.52 Other studies have indicated that obese individuals present with pathological plasma-dependent RBC aggregation.53 In this study, we also found a correlation between plasmatic factors and aggregation parameters after sleeve gastrectomy. These variations were correlated with an improvement in the fibrinogen level or plasma viscosity and the lipid pattern, which was the most unchanged after surgery. The correlation between cholesterol and LDL can slightly explain the increased t1/2 after surgery because hyperlipidaemia is now known to be a factor affecting erythrocyte © 2014 Macmillan Publishers Limited
Red blood cell aggregations change after sleeve gastrectomy M Wiewiora et al
aggregation.54 Fibrinogen is considered an essential factor for RBC aggregation in normal weight subjects. Maeda et al.55 showed that increasing fibrinogen concentrations lead to the accelerated aggregation of erythrocytes, most likely due to the increased bridging force among erythrocytes. It has also been shown that blood defibrinogenation reduces the extent of aggregation.34 Studies regarding the effects of fibrinogen on erythrocyte aggregation in obese patients were inconclusive. Solá et al.26,29 showed that the absence of reduced fibrinogen levels after weight loss was associated with a low-calorie diet in obese patients. The authors suggest that fibrinogen is not responsible for the aggregation processes in obese subjects because weight loss impacts the improvement in their RBC aggregation without changing their fibrinogen levels. On the other hand, some studies have demonstrated reduced fibrinogen levels that depend on the size of the weight loss after dieting24,56 and surgical treatments57 for morbidly obese patients. Our results indicated that fibrinogen levels are one of the most important factors influencing the reduction in erythrocyte hyperaggregation among obese individuals after surgery. This relationship confirmed a linear correlation between a reduced AI and lower fibrinogen levels after surgery. The results of multivariate regression revealed that fibrinogen and plasma viscosity are independent predictors influencing the aggregation index. The presented results suggest that improving the RBC aggregation behaviours among obese subjects with weight loss due to sleeve gastrectomy is associated with changes in the plasmatic factors, especially fibrinogen. These changes in erythrocyte rheology after weight reduction surgery may improve the blood flow conditions in the microcirculation. These results may suggest the necessity of further studies to evaluate the method of correcting RBC rheological disorders, especially in patients who qualify for bariatric surgery for the prevention of postoperative complications related to microcirculation disturbances. CONFLICT OF INTEREST The authors declare no conflict of interest.
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1355 12 Lowe GD, Ghafour IM, Belch JJ, Forbes CD, Foulds WS, MacCuish AC. Increased blood viscosity in diabetic proliferative retinopathy. Diabetes Res 1986; 3: 67–70. 13 Le Devehat C, Khodabandehlou T. Transcutaneous oxygen pressure and hemorheology in diabetes mellitus. Int Angiol 1990; 9: 259–262. 14 Toker S, Rogowski O, Melamed S, Shirom A, Shapira I, Berliner S et al. Association of components of the metabolic syndrome with the appearance of aggregated red blood cells in the peripheral blood. An unfavorable hemorheological finding. Diabetes Metab Res Rev 2005; 21: 197–202. 15 Guiraudou M, Varlet-Marie E, Raynaud de Mauverger E, Brun JF. Obesity-related increase in whole blood viscosity includes different profiles according to fat localization. Clin Hemorheol Microcirc 2013; 55: 63–73. 16 Brun JF, Varlet-Marie E, Raynaud de Mauverger E, Mercier J. Both overall adiposity and abdominal adiposity increase blood viscosity by separate mechanisms. Clin Hemorheol Microcirc 2011; 48: 257–263. 17 Levy Y, Elias N, Cogan U, Yeshurun D. Abnormal erythrocyte rheology in patients with morbid obesity. Angiology 1993; 44: 713–717. 18 Hitsumoto T. Factors affecting impairment of blood rheology in obese subjects. J Cardiol 2012; 60: 401–406. 19 Valensi P, Smagghue O, Pariès J, Velayoudon P, Lormeau B, Attali JR. Impairment of skin vasoconstrictive response to sympathetic activation in obese patients: influence of rheological disorders. Metabolism 2000; 49: 600–606. 20 Wiewiora M, Sosada K, Wylezol M, Slowinska L, Zurawinski W. Red blood cell aggregation and deformability among patients qualified for bariatric surgery. Obes Surg 2007; 17: 365–371. 21 Solá E, Vayá A, Martínez M, Moscardó A, Corella D, Santaolaria ML et al. Erythrocyte membrane phosphatidylserine exposure in obesity. Obesity (Silver Spring) 2009; 17: 318–322. 22 Wiewiora M, Slowinska–Lozynska L, Glück M, Piecuch J, Sosada K. Shear stress and flow dynamics of the femoral vein among obese patients who qualify for bariatric surgery. Clin Hemorheol Microcirc 2013; 54: 313–323. 23 Gelmini G, Coiro V, Manotti C, Delsignore R, Passeri M. Effect of diet and weight loss on whole blood filterability and plasma fibrinogen values in hypertensive obese postmenopausal women. Acta Diabetol Lat 1989; 26: 329–335. 24 Fanari P, Somazzi R, Nasrawi F, Ticozzelli P, Grugni G, Agosti R et al. Haemorheological changes in obese adolescents after short-term diet. Int J Obes Relat Metab Disord 1993; 17: 487–494. 25 Poggi M, Palareti G, Biagi R, Legnani C, Parenti M, Babini AC et al. Prolonged very low calorie diet in highly obese subjects reduces plasma viscosity and red cell aggregation but not fibrinogen. Int J Obes Relat Metab Disord 1994; 18: 490–496. 26 Solá E, Vayá A, Corella D, Santaolaria ML, España F, Estellés A et al. Erythrocyte hyperaggregation in obesity: determining factors and weight loss influence. Obesity (Silver Spring) 2007; 15: 2128–2134. 27 Valensi P, Paries J, Maheo P, Gaudey F, Attali JR. Erythrocyte rheological changes in obese patients: influence of hyperinsulinism. Int J Obes Relat Metab Disord 1996; 20: 814–819. 28 Solá E, Vayá A, Simó M, Hernández-Mijares A, Morillas C, España F et al. Fibrinogen, plasma viscosity and blood viscosity in obesity. Relationship with insulin resistance. Clin Hemorheol Microcirc 2007; 37: 309–318. 29 Solá E, Vayá A, Contreras T, Falcó C, Corella D, Hernández A et al. Effect of a hypocaloric diet on lipids and rheological profile in subjects with severe and morbid obesity. A follow-up study. Clin Hemorheol Microcirc 2004; 30: 419–422. 30 Wiewiora M, Slowinska L, Wylezol M, Pardela M, Kobielski A. Rheological properties of erythrocytes in patients suffering from morbid obesity. Examination with LORCA device. Clin Hemorheol Microcirc 2006; 34: 499–506. 31 Capuano P, Catalano G, Garruti G, Trerotoli P, Cicco G, Martines G et al. The effects of weight loss due to gastric banding and lifestyle modification on red blood cell aggregation and deformability in severe obese subjects. Int J Obes (Lond) 2012; 36: 342–347. 32 Rosenthal RJ; International Sleeve Gastrectomy Expert Panel, Diaz AA, Arvidsson D, Baker RS, Basso N et al. International Sleeve Gastrectomy Expert Panel Consensus Statement: best practice guidelines based on experience of >12,000 cases. Surg Obes Relat Dis 2012; 8: 8–19. 33 Baskurt OK, Boynard M, Cokelet GC, Connes P, Cooke BM, Forconi S et al. New guidelines for hemorheological laboratory techniques. Clin Hemorheol Microcirc 2009; 42: 75–97. 34 Hardeman MR, Dobbe JGG, Ince C. The Laser–assisted Optical Rotational Cell Analyser (LORCA) as red blood cell aggregometer. Clin Hemorheol Microcirc 2001; 25: 1–11. 35 Arend O, Wolf S, Jung F, Bertram B, Pöstgens H, Toonen H et al. Retinal microcirculation in patients with diabetes mellitus: dynamic and morphological analysis of perifoveal capillary network. Br J Ophthalmol 1991; 75: 514–518. 36 Monostori P, Baráth A, Fazekas I, Hódi E, Máté A, Farkas I et al. Microvascular reactivity in lean, overweight, and obese hypertensive adolescents. Eur J Pediatr 2010; 169: 1369–1374.
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1356 37 de Jongh RT, Serné EH, IJzerman RG, Jørstad HT, Stehouwer CD. Impaired local microvascular vasodilatory effects of insulin and reduced skin microvascular vasomotion in obese women. Microvasc Res 2008; 75: 256–262. 38 Willenberg T, Schumacher A, Amann-Vesti B, Jacomella V, Thalhammer C, Diehm N et al. Impact of obesity on venous hemodynamics of the lower limbs. J Vasc Surg 2010; 52: 664–668. 39 Mchedlishvili G. Basic factors determining the hemorheological disorders in the microcirculation. Clin Hemorheol Microcirc 2004; 30: 179–180. 40 Bishop JJ, Popel AS, Intaglietta M, Johnson PC. Rheological effects of red blood cell aggregation in the venous network: a review of recent studies. Biorheology 2001; 38: 263–274. 41 Bishop JJ, Nance PR, Popel AS, Intaglietta M, Johnson PC. Effect of erythrocyte aggregation on velocity profiles in venules. Am J Physiol Heart Circ Physiol 2001; 280: H222–H236. 42 Cokelet GR, Goldsmith HL. Decreased hydrodynamic resistance in the two-phase flow of blood through small vertical tubes at low flow rates. Circ Res 1991; 68: 1–17. 43 Bishop JJ, Nance PR, Popel AS, Intaglietta M, Johnson PC. Erythrocyte margination and sedimentation in skeletal muscle venules. Am J Physiol Heart Circ Physiol 2001; 281: H951–H958. 44 Ong PK, Namgung B, Johnson PC, Kim S. Effect of erythrocyte aggregation and flow rate on cell-free layer formation in arterioles. Am J Physiol Heart Circ Physiol 2010; 298: H1870–H1878. 45 Klitzman B, Duling BR. Microvascular hematocrit and red cell flow in resting and contracting striated muscle. Am J Physiol 1979; 237: H481–H490. 46 Namgung B, Ong PK, Johnson PC, Kim S. Effect of cell-free layer variation on arteriolar wall shear stress. Ann Biomed Eng 2011; 39: 356–359. 47 Ong PK, Jain S, Namgung B, Woo YI, Kim S. Cell-free layer formation in small arterioles at pathological levels of erythrocyte aggregation. Microcirculation 2011; 18: 541–551.
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48 Baskurt OK, Meiselman HJ. Erythrocyte aggregation: basic aspects and clinical importance. Clin Hemorheol Microcirc 2013; 53: 23–37. 49 Brun JF, Varlet-Marie E, Romain AJ, Raynaud de Mauverger E. Interrelationships among body composition, blood rheology and exercise performance. Clin Hemorheol Microcirc 2011; 49: 183–197. 50 Brun JF, Varlet-Marie E, Cassan D, Raynaud de Mauverger E. Blood rheology and body composition as determinants of exercise performance in female rugby players. Clin Hemorheol Microcirc 2011; 49: 207–214. 51 Dintenfass L. Autoregulation of blood viscosity in health and disease. Vascular Surg 1980; 14: 227–237. 52 Jung F, Roggenkamp HG, Ringelstein EB, Leipnitz G, Schneider R, Kiesewetter H et al. H. Effect of sex, age, body weight, and smoking on plasma viscosity. Klin Wochenschr 1986; 64: 1076–1081. 53 Samocha-Bonet D, Ben-Ami R, Shapira I, Shenkerman G, Abu-Abeid S, Stern N. Flow-resistant red blood cell aggregation in morbid obesity. Int J Obes Relat Metab Disord 2004; 28: 1528–1534. 54 Cicha I, Suzuki Y, Tateishi N, Maeda N. Effects of dietary triglycerides on rheological properties of human red blood cells. Clin Hemorheol Microcirc 2004; 30: 301–305. 55 Maeda N, Imaizumi K, Sekiya M, Shiga T. Rheological characteristics of desialylated erythrocytes in relation to fibrinogen-induced aggregation. Biochim Biophys Acta 1984; 776: 151–158. 56 Ditschuneit HH, Flechtner-Mors M, Adler G. Fibrinogen in obesity before and after weight reduction. Obes Res 1995; 3: 43–48. 57 Primrose JN, Davies JA, Prentice CR, Hughes R, Johnston D. Reduction in factor VII, fibrinogen and plasminogen activator inhibitor-1 activity after surgical treatment of morbid obesity. Thromb Haemost 1992; 68: 396–399.
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ORIGINAL ARTICLE
Impact of sleeve gastrectomy on red blood cell aggregation: a 12-month follow-up study M Wiewiora1, J Piecuch1, M Glück1, L Slowinska-Lozynska2 and K Sosada1 OBJECTIVE: To investigate the effects of weight loss due to laparoscopic sleeve gastrectomy (LSG) on erythrocyte aggregation and the relationship of anthropometric and plasmatic factors, such as plasma viscosity, fibrinogen and lipids, with erythrocyte aggregation. DESIGN AND SUBJECTS: The RBC aggregation and kinetics of the red blood cell aggregation were performed by the Laser-assisted Optical Rotational Cell Analyser (LORCA). Before the LSG and 6 and 12 months after the LSG, we evaluated the aggregation index (AI), amplitude (AMP) and aggregation half-time (t1/2), plasma viscosity, fibrinogen, glucose and lipids patterns in 15 non-diabetic obese subjects. RESULTS: The static and kinetic parameters of aggregation in obese patients at each time point after bariatric weight loss surgery were calculated and significant differences were observed at 12 months after surgery. AI and AMP decreased from 69.81 ± 5.12% and 27.43 ± 2.9 a.u. at baseline to 64.91 ± 5.94% and 22.15 ± 4.3 a.u. 12 months after surgery, respectively. The t1/2 increased from 1.7 (1.32–2.24) s at baseline compared with 2.02 (1.68–2.42) s at 12 months after the surgery. Plasma viscosity and fibrinogen decreased from 1.50 ± 0.093 mPa s and 3.0 ± 0.41 g l− 1 at baseline to 1.407 ± 0.062 mPa s and to 2.66 ± 0.25 g l − 1 12 months after surgery, respectively. AI correlated positively with BMI (r = 0.74, P = 0.001), waist circumference (r = 0.68, P = 0.005), fibrinogen (r = 0.52, P = 0.045) and plasma viscosity (r = 0.76, P = 0.001) and negatively with percentages of weight lost after surgery (r = − 0.54, P = 0.034). Multivariate analyses found that the BMI, fibrinogen and plasma viscosity independently influenced the AI. CONCLUSION: The study demonstrated that weight loss due to restrictive bariatric surgery can beneficially affect red cell aggregation parameters. The improvement of the RBC aggregation behaviours among obese subjects with weight loss due to LSG was associated with changes in plasmatic factors, especially fibrinogen. International Journal of Obesity (2014) 38, 1350–1356; doi:10.1038/ijo.2014.17 Keywords: red cell aggregation; sleeve gastrectomy; bariatric surgery
INTRODUCTION Obesity is associated with an increased risk of many medical problems, leading to increased morbidity1 and mortality.2 Studies have shown that disorders of some haemorheological parameters are correlated with comorbid pathologies associated with morbid obesity. Erythrocyte rheological changes have been observed in patients with cardiovascular diseases,3–5 hypertension6–8 and diabetes mellitus9–13 or metabolic syndrome.14 There is a recent literature showing that the obesity-associated increase in whole blood viscosity exhibits different profiles according to fat localisation.15,16 These data suggest that abdominal fat increases the blood viscosity due to haematocrit elevation, but overall adiposity is associated with increased plasma viscosity and red cell aggregation. However, other authors have shown the absence of improvement in abnormal erythrocyte rheology in obese women after short-term significant weight loss associated with a 10-day zero-calorie diet.17 Another recent study has not confirmed the correlation between blood rheology evaluated by the microchannel array flow analyser and BMI or WHR in male or female obese subjects.18 The author indicated that inflammation, oxidative stress and lifestyle habits are more important factors for the impairment of blood rheology than the degree of adiposity in obese individuals.
Haemorheological alterations in obesity have been reported by various groups, including disturbances of the rheological behaviour of blood, such as enhanced RBC aggregation. Erythrocyte hyperaggregation and a decrease in erythrocyte deformability have been well documented in obese patients.19–22 The impacts of a hypocaloric diet on the haemorheology of obese patients have been reported in a number of studies. Most of these studies showed that weight loss after dieting in obese patients contributed to normalising of the rheological profile with a corresponding improvement in the plasma viscosity, blood viscosity and red cell aggregation or deformability, depending on the size of weight loss.23–26 On the other hand, some studies have shown an absence of improvement in rheological parameters, including RBC aggregation, after weight loss associated with a low-calorie diet.27,16 Other authors have presented that a very low-calorie diet reduced erythrocyte aggregation at one month, but a prolonged low-calorie diet did not provide any additional benefit in weight or red cell aggregation, both of which returned to their basal values after 3 months of follow-up.29 Research on the impact of diet on haemorheology indicated a beneficial effect of weight loss on rheological profiles, as erythrocyte aggregation depends on the amount of weight lost and its long-term maintenance. The influence of bariatric surgery
1 Department of General and Bariatric Surgery and Emergency Medicine in Zabrze, Medical University of Silesia, Katowice, Poland and 2Chair and Department of Biophysics in Zabrze, Medical University of Silesia, Katowice, Poland. Correspondence: Dr M Wiewiora, Department of General and Bariatric Surgery and Emergency Medicine, Medical University of Silesia, ul. Sklodowskiej-Curie10, Zabrze 41-800, Poland. E-mail: [email protected] Received 20 October 2013; revised 6 January 2014; accepted 17 January 2014; accepted article preview online 31 January 2014; advance online publication, 25 February 2014
Red blood cell aggregations change after sleeve gastrectomy M Wiewiora et al
1351 on haemorheological parameters has been investigated in few studies up to now.30,31 To the best of our knowledge, the effects of sleeve gastrectomy on the rheological properties of blood in severely obese subjects have not yet been established. The aim of this study was to evaluate the effects of weight loss due to laparoscopic sleeve gastrectomy on erythrocyte aggregation at a 12-month follow-up. MATERIALS AND METHODS Patient characteristics We studied 17 morbidly obese patients who underwent sleeve gastrectomy. Of the 17 patients who were included in the study, 15 patients were finally analysed. Thrombophlebitis and pulmonary embolism occurred in one male, and one female had gynaecological disturbances requiring long-term hormonal therapy. Both these patients were excluded from subsequent postoperative comparisons. There were 5 males and 10 females in the study, with a mean age of 37.6 ± 7.12 years, mean weight of 141.77 ± 17.49 kg and a mean body mass index (BMI) of 49.0 ± 4.66 kg m −2. The factors used as exclusion criteria included those that could potentially influence the observed rheological blood parameters. Exclusion criteria included smoking, diabetes mellitus, thyroid disease, chronic kidney disease, anaemia and abnormal coagulation parameters, uncontrolled hypertension, history of leg vein thrombosis, antithrombotic or/and oestrogen or/and contraceptive therapy (o3 months before examination), hypolipemic treatment and lack of patient consent to participate. The exclusion criteria, which were related to the use of anticoagulants and antiplatelet agents, were applied to a period of 3 months before the study date. The study protocol was accepted by the ethical committee of the Medical University of Silesia, and all participants provided written consent. Patients enroled into the study underwent laparoscopic sleeve gastrectomy. In this study, laparoscopic sleeve gastrectomy was performed according to a commonly used technique.32 The greater curvature vessels were divided using the LigaSure device (Covidien, Mansfield, MA, USA). A longitudinal resection of the stomach was achieved using a linear cutting stapler (Echelon Flex 60 Endopath, Ethicon Endosurgery, Guaynabo, PR, USA), beginning from the point 5 to 6 cm proximal to the pylorus and continuing to the Angle of His and tightly abutting the bougie (a 36French), which had been placed transorally into the pyloric channel along the lesser curvature. Patients were followed for one year following the procedure. The patients were weighed, examined and interviewed by the surgeon preoperatively and at 1, 6 and 12 months after the operation. Blood was drawn for biochemical and rheological measurements preoperatively and at 6 and 12 months after the operation. Data from morbidly obese subjects were compared with those from control groups before surgery. The gender distribution and ages were similar in the obese and control groups. The control group consisted of 20 non-obese people without arterial hypertension, diabetes mellitus or any of the other above-listed features.
Haemorheological and biochemical measurements Blood samples were collected from the cubital vein with a syringe for biochemical examination and then anticoagulated with K3EDTA (1.5 mg ml− 1) for rheological tests.33 The rheological tests were performed at a stable temperature of 37 °C within two hours after the blood was collected. Plasma viscosity measurements were performed using a Brookfield DV-II+ (Wells-Brookfield, Brookfield Engineering Laboratories, Middleboro, MA, USA) cone-plate viscometer at shear rates of 900 s-1. The RBC aggregation and kinetics of the red blood cell aggregation were performed by the Laser-assisted Optical Rotational Cell Analyser—LORCA (Mechatronics, Zwaag, The Netherlands). The instrument and the methodological aspects have been described in detail elsewhere.34 The following parameters specific to the aggregation process were estimated: the aggregation index (AI in %), amplitude (in a.u.) and aggregation half-time (t1/2 in s), which express the kinetics of the aggregation process. Fibrinogen levels were measured using Clauss clotting method. The concentration of total cholesterol (T-CHOL), high-density lipoproteins (HDL), triglycerides (TG) and glucose levels were evaluated using an Integra 400 Plus Autoanalyzer (Roche Diagnostic, Mannheim, Germany). Low-density lipoproteins (LDL) were calculated using Friedewald formula. © 2014 Macmillan Publishers Limited
Statistical analysis Continuous variables are presented as the means ± s.d. or the median with the inter-quartile range, if not normally distributed. Categorical variables are presented as absolute numbers and percentages. The Shapiro–Wilk test was used for all continuous variables to test for their normal distribution. Differences between the morbidly obese and control groups before surgery were assessed using the unpaired Student’s t-test and the Mann–Whitney U-test for non-normally distributed data. Fisher’s exact test was performed to compare differences among the categorical data. Differences in each variable at the three time points (before surgery, 6 months and 12 months after surgery) were calculated by analysis of variance (ANOVA) tests, followed by Tukey’s post hoc or Friedman ANOVA tests and then Scheffe’s post hoc tests for non-normally distributed data. The paired Student’s t-test was performed to compare the differences of the data at 6 months and 12 months after surgery. The associations among continuous variables were tested using Pearson’s correlation or Spearman’s rank correlation. Independent predictors that influenced the aggregation index after surgery were determined by a multivariate regression model using the stepwise selection of anthropometric and biochemical parameters, with an entry criterion of P o0.05. Variables considered to be potential predictors for multivariate modelling were identified by univariate analyses and subsequently selected by stepwise backward selection. A P-value o0.05 was considered to be significant. This statistical analysis was performed using Statistica 10 (StatSoft Inc., Tulsa, OK, USA).
RESULTS The baseline characteristics of the study population and their comparisons with the control group are presented in Table 1. Anthropometric parameters decreased at each time point after surgery (Table 2). The percentages of excess weight lost at 6 months and 12 months after surgery were 46.19 ± 14.01 and 58.3 ± 21.77, respectively (P = 0.0048). The percentages of weight
Table 1. Baseline characteristics of obese patients and control participants Morbid obesity, N = 15 Gender Male Female
5 (33.3%) 10 (76.7%)
Age (years) Weight (kg) BMI (kg m −2) WHR AI (%) AMP (a.u.) t1/2 (s) Plasma viscosity (mPa s) Fibrinogen (g l− 1) SBP (mmHg) DBP (mmHg) FPG (mmol l − 1) T-CHOL (mg dl − 1) LDL (mg dl − 1) HDL (mg dl − 1) TG (mg dl − 1)
Control, N = 20 6 (30%) 14 (70%)
37.6 ± 7.12 36.7 ± 8.9 141.77 ± 17.49 68.32 ± 10.36 49.0 ± 4.66 23.7 ± 1.65 1.04 ± 0.12 0.83 ± 0.06 69.81 ± 5.12 56.43 ± 6.9 27.43 ± 2.9 23.41 ± 3.02 1.7 (1.32–2.24) 3.06 (2.15–3.78) 1.50 ± 0.093 1.37 ± 0.08 3.0 ± 0.41 2.33 ± 0.39 140 (135–140) 120 (110–130) 90 (80–90) 75 (70–80) 5.31 ± 0.66 4.63 ± 0.57 195.66 ± 37.94 200.36 ± 39.4 123.66 ± 32.82 124.82 ± 36.15 43.9 ± 11.74 67.84 ± 15.8 145 (120–167) 68 (54–100)
P-value
0.574 0.571 0.803 o0.0001 o0.0001 o0.0001 o0.0001 0.00038 0.00011 0.00012 o0.0001 0.00010 0.01490 0.00262 0.762 0.921 o0.0001 o0.0001
Abbreviations: AI, aggregation index; AMP, amplitude; a.u., arbitrary units; BMI, body mass index; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HDL, high-density lipoproteins cholesterol; LDL, low-density lipoproteins cholesterol; SBP, systolic blood pressure; t1/2, aggregation half-time; T-CHOL, total cholesterol; TG, triglycerides; WHR, waist-to-hip circumference ratio. Data are presented as the means ± s.d. or median (inter-quartile range) for continuous variables or as prevalences for categorical data. Group differences were calculated using the unpaired Student’s t-test or the Mann–Whitney U-test for non-normally distributed data and the Fisher’s exact test for categorical data.
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Red blood cell aggregations change after sleeve gastrectomy M Wiewiora et al
1352 Table 2.
Differences in each variable before surgery and at each time point after surgery Baseline, N = 15
Weight (kg) BMI (kg m −2) Waist circumference (cm) Hip circumference (cm) WHR AI (%) AMP (a.u.) t1/2 (s) Plasma viscosity (mPa s) Fibrinogen (g l − 1) SBP (mmHg) DBP (mmHg) FPG (mmol l − 1) T-CHOL (mg dl − 1) LDL (mg dl − 1) HDL (mg dl − 1) TG (mg dl − 1)
141.77 ± 17.49 49.0 ± 4.66 136.93 ± 12.98 131.8 ± 13.02 1.04 ± 0.12 69.81 ± 5.12 27.43 ± 2.9 1.7 (1.32–2.24) 1.50 ± 0.093 3.0 ± 0.41 140 (135–140) 90 (80–90) 5.31 ± 0.66 195.66 ± 37.94 123.66 ± 32.82 43.9 ± 11.74 145 (120–167)
6 Months, N = 15
105.0 ± 8.79 36.69 ± 3.98 109.76 ± 12.3 125.53 ± 16.18 0.88 ± 0.12 65.78 ± 5.18 23.91 ± 4.5 1.72 (1.64–1.98) 1.480 ± 0.104 3.11 ± 0.33 130 (120–140) 80 (80–90) 5.21 ± 0.45 184.5 ± 46.74 110.32 ± 34.3 50.92 ± 13.15 96 (81.5–137)
12 Months, N = 15
98.93 ± 8.45 34.47 ± 4.19 108.7 ± 10.96 124.53 ± 10.86 0.87 ± 0.08 64.91 ± 5.94 22.15 ± 4.3 2.02 (1.68–2.42) 1.407 ± 0.062 2.66 ± 0.25 120 (110–140) 80 (80–90) 5.04 ± 0.39 200.53 ± 48.85 119.86 ± 39.22 58.47 ± 13.71 101 (68–164)
P-value 6 Months vs baseline
12 Months vs baseline
0.000131 0.000122 0.000123 0.440623 0.001632 0.138123 0.083863 0.777736 0.819185 0.668237 0.091627 0.978274 0.869696 0.795638 0.626328 0.346560 0.108313
0.000122 0.000122 0.000122 0.308368 0.000971 0.046991 0.003938 0.09336 0.016324 0.029582 0.003734 0.981613 0.344446 0.952138 0.962575 0.009930 0.167612
Abbreviations: AI, aggregation index; AMP, amplitude; a.u., arbitrary units; BMI, body mass index; DBP, diastolic blood pressure; FPG, fasting plasma glucose; HDL, high-density lipoproteins cholesterol; LDL, low-density lipoproteins cholesterol; SBP, systolic blood pressure; t1/2, aggregation half-time; T-CHOL, total cholesterol; TG, triglycerides; WHR, waist-to-hip circumference ratio. Data are the means ± s.d. or medians (inter-quartile range) for continuous variables. Group differences at the three time points (before surgery, 6 months and 12 months after surgery) were calculated by the analysis of variance.
lost also significantly changed at each time point after sleeve gastrectomy, with 23.76 ± 6.99 and 29.39 ± 9.47 at 6 months and 12 months after surgery, respectively (P = 0.0091). The haemorheological parameters also changed postoperatively at each time point (Table 2). Significant differences were observed for AI, which decreased from 69.81 ± 5.12% at baseline compared with 64.91 ± 5.94% at 12 months after surgery (P = 0.046) and for amplitude, which decreased from 27.43 ± 2.9 a.u. at baseline to 22.15 ± 4.3 a.u. at 12 months after surgery (P = 0.0039). Similar decreasing trends were observed for plasma viscosity and fibrinogen concentration. Plasma viscosity significantly decreased from 1.50 ± 0.093 mPa s at baseline to 1.407 ± 0.062 mPa s at 12 months after surgery (P = 0.016). Fibrinogen significantly decreased from 3.0 ± 0.41 g l − 1 at baseline to 2.66 ± 0.25 g l − 1 at 12 months after surgery (P = 0.029). The t1/2 tended to be higher at baseline compared with 12 months after surgery, from 1.7 (1.32–2.24) s to 2.02 (1.68–2.42) s (P = 0.09). Changes in the lipid patterns at each time point before and after surgery were not significant, except for HDL (Table 2). The HDL increased from 43.9 ± 11.74 mg dl − 1 at baseline to 58.47 ± 13.71 mg dl − 1 at 12 months after surgery (P = 0.009). The correlation between AI and the anthropometric parameters is presented in Figure 1. AI correlated positively with BMI (r = 0.7470, P = 0.001) and waist circumference (r = 0.6812, P = 0.005) and negatively with %WL (r = − 0.5490, P = 0.034). The correlation between AI and fibrinogen (r = 0.5236, P = 0.045), T-CHOL (r = 0.5555, P = 0.032) and plasma viscosity (r = 0.7613, P = 0.001) is presented in Figure 2. Univariate analyses revealed six potential predictors influencing the AI and the t1/2. These predictors included the BMI, %WL, waist circumference, fibrinogen, T-CHOL and plasma viscosity (Tables 3 and 4). Multivariate analyses found BMI (β = 0.7477, P = 0.0427; Table 3), fibrinogen (β = 0.3938, P = 0.0294; Table 4) and plasma viscosity (β = 0.4739, P = 0.0213; Table 4) to be variables that independently influenced the AI. DISCUSSION Haemorheological disturbances may determine the quality of the blood flow in both the microcirculation network and in macrocirculation, especially in obese individuals.35–38 It has been clearly International Journal of Obesity (2014) 1350 – 1356
shown that RBC aggregation has an important role in determining the low shear blood viscosity39 and contributes to blood flow.40,41 Generally, increasing blood viscosity with increasing RBC aggregates forms rouleaux structures with larger geometries at low shear rates. Studies have shown that RBC aggregation promotes the axial accumulation of RBCs in ex vivo investigations into the tube flow42 and microcirculation of animal models,43,44 resulting in a two-phase flow consisting of a core of aggregates and a cell-free layer. The ability of RBCs to aggregate into the slow-moving plasma layer is most important in determining the effects of this hydrodynamic resistance at low flow rates in tubes42 and capillaries,45 as the dimension of this effect increases with red cell hyperaggregation. Other authors have indicated that red blood cell aggregation may alter the cell-free layer variability, especially at low shear rates.46,47 The effect of RBC aggregation on tissue blood flow is not one-sided, as the haemodynamic consequences of RBC aggregation can affect the amount of tissue perfusion resulting from several interrelated mechanisms. These mechanisms include the axial accumulation of RBC, viscosity and resistance in the cell-free layer and the haematocrit of the microvessels or wall shear stress, both of which depend on the behaviour of the RBC aggregates. Axial accumulation is also the primary mechanism underlying the Fahraeus–Lindqvist effect, which refers to the decrease in the viscosity of blood with decreasing vessel radius, as observed in vessels less than 500 μm in diameter. Plasma skimming and the Fahraeus effect both contribute to the significantly lower microvascular haematocrit compared with arterial or venous haematocrit. This reduced microvessel haematocrit contributes to a lower than expected haemodynamic resistance. Thus, the effect of enhanced red blood cell aggregation on microcirculatory blood flow is biphasic and some degree of increased RBC aggregation does not always induce significant microcirculatory blood flow disturbances. The hyperaggregation of RBCs result in a decreased tissue blood perfusion and may also increase the risk of thrombosis.48 These results confirmed that obesity is associated with alterations in RBC rheology, expressed by an increased extent of total aggregation and the spontaneous ability to aggregate. Alterations in the kinetics of RBC aggregation expressed by shortening t1/2 indicate that RBCs in obese individuals form aggregates and rouleaux © 2014 Macmillan Publishers Limited
Red blood cell aggregations change after sleeve gastrectomy M Wiewiora et al
1353
Figure 1. Correlation between AI and anthropometric parameters: (a) with BMI; (b) with waist circumference and (c) with %WL. The associations among the variables were tested using Pearson’s correlations.
Figure 2. Correlation between AI and biochemical parameters: (a) with fibrinogen; (b) with T-CHOL and (c) with plasma viscosity. The associations among the variables were tested using Pearson’s correlations.
within a shorter time after their disaggregation than in normalweight individuals.34 A recent literature review concerning the relationships among body composition, blood rheology and exercise performance showed that red cell aggregation is correlated to fat mass not only in obese or overweight individuals but also within a physiological range of fat mass.49 Observations of rugby players may suggest that this proportionality between fat mass and erythrocyte aggregability is not an essentially pathologic mechanism but a physiological relationship.49,50 Other authors
have shown that the obesity-associated increase in whole blood viscosity occurs through different mechanisms on the basis of fat localisation.15 The authors speculated that changes in blood rheology, such as moderate increases in RBC aggregation and deformability or plasma viscosity related to some degree of increased fat mass are physiological consequences of sedentarity and may be an adaptive mechanism beneficial for circulation. However, at a critical capillary radius, the increase in the blood viscosity depends on the rigidity of the blood cells,
© 2014 Macmillan Publishers Limited
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Red blood cell aggregations change after sleeve gastrectomy M Wiewiora et al
1354 Table 3.
Regression analysis of the potential anthropometric predictors of influences on the aggregation parameters at 12 months after sleeve gastrectomy Variable
Univariate regression β
SEβ
P-value
0.7894 −0.5489 −0.3962 0.6811 0.1635 0.4919
0.17
0.00046 0.0340 0.143 0.00517 0.560 0.0624
AI BMI %WL %EWL Waist circumference Hip circumference WHR
Multivariate regression
0.25 0.2 0.27 0.24
BMI % WL Waist circumference
β
SEβ
P-value
R2
0.7477 0.1646 0.2181
0.3 0.28 0.28
0.0427 0.5694 0.4569
0.55
Abbreviations: BMI, body mass index; EWL, excess weight lost; R2, coefficient of determination; SEβ, standard error of β; WL, weight lost; WHR, waist-to-hip circumference ratio. P-values o0.05 are shown in bold.
Table 4.
Regression analysis of the potential biochemical predictors of influences on the aggregation index (AI) at 12 months after sleeve gastrectomy Variable
SBP DBP Fibrinogen FPG T-CHOL LDL HDL TG Plasma viscosity
Univariate regression
Multivariate regression
β
SEβ
P-value
0.3751 0.4058 0.5236 0.1591 0.5554 0.4402 0.3340 0.3038 0.7612
0.27 0.27 0.23 0.27 0.23 0.24 0.26 0.26 0.17
0.206 0.168 0.0451 0.570 0.0315 0.10 0.223 0.27 0.0009
Fibrinogen T-CHOL Plasma viscosity
β
SEβ
P-value
R2
0.3938 0.3599 0.4739
0.15 0.16 0.17
0.0294 0.0553 0.0213
0.703
Abbreviations: DBP, diastolic blood pressure; FPG, fasting plasma glucose; HDL, high-density lipoproteins cholesterol; LDL, low-density lipoproteins cholesterol; R2, coefficient of determination; SBP, systolic blood pressure; SEβ, standard error of β; T-CHOL, total cholesterol; TG, triglycerides. P-values o 0.05 are shown in bold.
RBC aggregation and other rheological properties of the blood.51 If rheological disorders have reached critical levels, resistance to flow may increase. In this study, we demonstrated that weight loss owing to restrictive bariatric surgery affects red cell aggregation parameters. We found changes in the static and kinetic parameters of aggregation in obese patients at each time point after bariatric weight loss surgery, but significant differences were only observed at 12 months after surgery. We observed a decrease in extent of aggregation and an elevated aggregation half-time, which indicate that spontaneous ability to aggregate was reduced, compared with baseline values. These findings also suggest that the beneficial effects of restrictive bariatric surgery on the hyperaggregation of RBCs are associated with obesity, depending on the size of the weight loss in the postoperative period. Most studies that were concerned with the influence of a hypocaloric diet on RBC aggregation in obese patients reported that weight loss after dieting in obese patients normalised the aggregation of the RBCs, effecting a corresponding improvement in the erythrocyte aggregation index.24–26 Other authors have shown the absence of improvement in rheological parameters, including RBC aggregation, after weight loss associated with a low-calorie diet.27,28 Sola et al.29 showed that a very low-calorie diet of 458 kcal per day reduced erythrocyte aggregation at one month, but a prolonged low-calorie diet providing 1500 kcal per day did not provide any additional benefit for red cell aggregation, which returned to its basal value at 3 months follow-up. Weight loss surgery is able to induce a long-term normalisation of RBC aggregation in obese subjects because it is more effective in weight control than various diets. To our knowledge, the influence International Journal of Obesity (2014) 1350 – 1356
of bariatric surgery on haemorheological parameters has been investigated in two previous papers. In these previous papers, vertical-banded gastroplasty was shown to induce some beneficial changes in the level of RBC aggregation.30 In a recent study, Capuano et al.31 observed a similarly beneficial effect of weight loss due restrictive bariatric procedures. The authors found a reduction in the AI and a slight increase in the t1/2 of obese subjects 6 months after adjustable gastric banding, but they did not analyse the impact of the evaluated anthropometric and biochemical parameters on erythrocyte aggregation. We found similar changes specific to the RBC aggregation process parameters at 12 months after sleeve gastrectomy. This might be explained by the fact that, in the study performed by Capuano et al., obese subjects underwent gastric restrictive bariatric surgery followed by a programme of lifestyle changes, including education on a Mediterranean diet and daily moderate exercise. We found not only a significant improvement in the rheological parameters but also an improved plasma viscosity and fibrinogen level at 12 months after surgery. It has been found that obesity is associated with plasma hyperviscosity.52 Other studies have indicated that obese individuals present with pathological plasma-dependent RBC aggregation.53 In this study, we also found a correlation between plasmatic factors and aggregation parameters after sleeve gastrectomy. These variations were correlated with an improvement in the fibrinogen level or plasma viscosity and the lipid pattern, which was the most unchanged after surgery. The correlation between cholesterol and LDL can slightly explain the increased t1/2 after surgery because hyperlipidaemia is now known to be a factor affecting erythrocyte © 2014 Macmillan Publishers Limited
Red blood cell aggregations change after sleeve gastrectomy M Wiewiora et al
aggregation.54 Fibrinogen is considered an essential factor for RBC aggregation in normal weight subjects. Maeda et al.55 showed that increasing fibrinogen concentrations lead to the accelerated aggregation of erythrocytes, most likely due to the increased bridging force among erythrocytes. It has also been shown that blood defibrinogenation reduces the extent of aggregation.34 Studies regarding the effects of fibrinogen on erythrocyte aggregation in obese patients were inconclusive. Solá et al.26,29 showed that the absence of reduced fibrinogen levels after weight loss was associated with a low-calorie diet in obese patients. The authors suggest that fibrinogen is not responsible for the aggregation processes in obese subjects because weight loss impacts the improvement in their RBC aggregation without changing their fibrinogen levels. On the other hand, some studies have demonstrated reduced fibrinogen levels that depend on the size of the weight loss after dieting24,56 and surgical treatments57 for morbidly obese patients. Our results indicated that fibrinogen levels are one of the most important factors influencing the reduction in erythrocyte hyperaggregation among obese individuals after surgery. This relationship confirmed a linear correlation between a reduced AI and lower fibrinogen levels after surgery. The results of multivariate regression revealed that fibrinogen and plasma viscosity are independent predictors influencing the aggregation index. The presented results suggest that improving the RBC aggregation behaviours among obese subjects with weight loss due to sleeve gastrectomy is associated with changes in the plasmatic factors, especially fibrinogen. These changes in erythrocyte rheology after weight reduction surgery may improve the blood flow conditions in the microcirculation. These results may suggest the necessity of further studies to evaluate the method of correcting RBC rheological disorders, especially in patients who qualify for bariatric surgery for the prevention of postoperative complications related to microcirculation disturbances. CONFLICT OF INTEREST The authors declare no conflict of interest.
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