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Red blood cell distribution width is not related with inflammatory parameters in morbidly obese patients
Clinical Biochemistry 47 (2014) 464–466
Contents lists available at ScienceDirect
Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem
Short Communication
Red blood cell distribution width is not related with inflammatory parameters in morbidly obese patients Amparo Vayá a,⁎, Rafael Alis b,c, Antonio Hernandez-Mijares d, Eva Solá d, Rosa Cámara e, Leonor Rivera a, Marco Romagnoli b,f, Begoña Laiz a a
Hemorheology and Haemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain Universitary Research Institute “Dr. Viña Giner”, Molecular and Mitochondrial Medicine, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain Faculty of Medicine, Catholic University of Valencia "San Vicente Mártir", Valencia, Spain d Endocrinology Service, Dr. Peset University Hospital, Valencia, Spain e Endocrinology Service, La Fe University Hospital, Valencia, Spain f Department of Physical Education and Sports, Catholic University of Valencia "San Vicente Mártir", Valencia, Spain. b c
a r t i c l e
i n f o
Article history: Received 10 October 2013 Received in revised form 27 December 2013 Accepted 17 January 2014 Available online 1 February 2014 Keywords: Obesity Inflammation Red blood distribution width Anemia
a b s t r a c t Objective: Red blood cell distribution width (RDW) is a hematological parameter that has been studied in several clinical settings and has been found to be related to both anemia and inflammatory status. As obesity is related to increased inflammatory pattern, we aimed to analyze the RDW in this setting. Methods: We determined hematological and inflammatory parameters in morbidly obese patients before bariatric surgery (n = 142) and normo-weight controls (n = 144). Results: RDW was higher in patients than in controls (p b 0.001), along with C-reactive protein (p b 0.001) and fibrinogen, (p b 0.001) while hemoglobin (p = 0.026), serum iron (p b 0.001), MCH (p = 0.002) and MCHC (p b 0.001) were lower in morbidly obese patients. The logistic correlation analysis revealed that only low serum iron (b62 μg/dL) and MCH (b 28.14 pg) levels were associated with RDW N 14% (OR 7.61, 95% CI: 1.93–30.04, p = 0.004; OR 5.67, 95% CI: 1.98–16.24, p = 0.001; respectively). Conclusions: These data indicate that the elevated RDW in morbidly obese patients reflects a mild red blood cell hypochromia that does not relate to inflammatory parameters, but to hyposideremia and, consequently, to lower erythrocyte indices, possibly as a result of being on a very low-calorie diet before bariatric surgery. Therefore, RDW should not be considered as an inflammatory marker in this clinical setting. Crown Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Introduction The association of red blood distribution width (RDW) with several clinical settings has been thoroughly explored in recent years. High RDW has been linked with autoimmune diseases [1], cardiovascular events [2] or infectious processes [3]. It has also been shown that the activity of pro-inflammatory cytokines causes a dysregulation of iron homeostasis, inhibits the proliferation of erythroid progenitor cells and impairs the erythropoietin-gene expression [4], leading to increased RDW. As obese patients present an elevated inflammatory status [5,6], it may be an interesting clinical setting to explore the association of RDW with inflammatory parameters. In fact, a recent study reported that obese adolescents show elevated RDW and, no overweight, but nutritional changes cause elevated RDW in an animal model [7]. Moreover, it has been shown that higher RDW is associated with a globally unfavorable lipid profile [8]. To further investigate this issue, we aimed to
⁎ Corresponding author at: Hemorheology and Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Avda. de Campanar, 21, 46009 Valencia, Spain. Fax: +34 963862714. E-mail address: [email protected] (A. Vayá).
study RDW values along with hematological and inflammatory parameters in morbidly obese patients before bariatric surgery. Material and methods Patients The patient group consisted of 142 morbidly (BMI N 40 kg/m2) obese patients (101 women, 41 men). Patients attended the Endocrinology Services at the La Fe and the Doctor Peset University Hospitals (Valencia, Spain) between 2009 and 2012. Some participated in the study published by our group in 2010 [9]. The control group comprised 144 healthy normal-weight (BMI b 30 kg/m2) volunteers (94 women, 50 men), consisting of non-consanguineous relatives or friends of patients, who were age- and sex-matched. The inclusion of patients and controls in the study was performed simultaneously, as sampling and analytical testing. Informed consent from all the participants and approval from La Fe University Hospital's Ethics Committee were obtained. This work complies with the principles of the Declaration of Helsinki. The exclusion criteria were organic, malignant, hematological, infectious or inflammatory disease, previous history of ischemic heart disease
0009-9120/$ – see front matter. Crown Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clinbiochem.2014.01.020
A. Vayá et al. / Clinical Biochemistry 47 (2014) 464–466
or stroke, previous thrombo-embolism, treatment with rheological drugs and secondary obesity (hypothyroidism, Cushing syndrome).
465
Table 2 Predictors for high RDW (≥14%). Crude
Laboratory methods Venous blood was drawn from the antecubital vein between 8 and 10 a.m. after 12 h of fasting with a minimum stasis. Basic hematological parameters were determined by a Sysmex XE-2100 (Roche Diagnostics S.L., Barcelona, Spain). Fibrinogen was performed in an ACL-TOP autoanalyzer (Instrumentation Laboratory, Milan, Italy) using coagulometric techniques. C-reactive protein (CRP) was determined by immunoturbidity and iron by colorimetry in an Olympus AU 5430 autoanalyzer.
CRP ≥ 5.73 (mg/L) Fibrinogen ≥ 369 (mg/dL) Leukocytes ≥ 7.64 (103/μL) Neutrophils ≥ 4.66 (103/μL) Hemoglobin b 12.88 (g/dL) Fe b 62 (μg/dL) MCV b 83.78 (fL) MCH b 28.24 (pg)
Adjusted
OR
95% CI
P
OR
95% CI
Pa
1.71 1.17 1.32 1.53 5.56 8.25 7.40 8.50
0.83–3.52 0.57–2.39 0.67–2.63 0.76 3.06 2.16–14.34 3.67–18.57 2.56–21.36 3.72–19.41
0.149 0.667 0.426 0.233 b0.001 b0.001 b0.001 b0.001
1.17 0.52 0.62 2.51 2.98 5.67 0.80 7.62
0.41–3.32 0.19–1.47 0.16–2.42 0.63 10.11 0.87–10.25 1.98–16.24 0.15–4.19 1.93–30.05
0.767 0.219 0.491 0.194 0.083 0.001 0.790 0.004
RDW: red blood distribution width, CRP: C-reactive protein, MCV: mean corpuscular volume, MCH: mean corpuscular hemoglobin. a Adjusted for all the others parameters.
Statistical analysis All the continuous variables were checked for normal distribution with the Kolmogorov–Smirnov test. CRP and fibrinogen were logtransformed to improve normality for statistical testing. A t-test for independent measures was used to compare the mean values in the continuous variables between obese patients and controls. Chi square tests were conducted to compare the percentages in dichotomic variables. Pearson' correlation coefficients were calculated to explore the crude relationship between continuous variables. When data were not normally distributed, correlation analyses were performed by Spearman's correlation coefficient (ρ). A logistic regression analysis was applied to estimate the unadjusted and multivariate-adjusted odds ratios (OR) and the 95% confidence intervals (CI) for independent variables on the risk for high RDW N 14%. The cut-off points for the dependent and independent variables were calculated from the mean values plus or minus one standard deviation (SD) of control subjects. Data are expressed as mean ± SD for normally distributed data and as median (min–max) for non-normally distributed data. P values of b0.05 were considered statistically significant. The statistical analysis was performed using SPSS version 15 (SPSS inc. Chicago, IL, USA). Results Table 1 summarizes the baseline characteristics of morbidly obese patients and control subjects. Inflammatory parameters (CRP, fibrinogen, leukocytes and neutrophils) were higher in patients, while serum iron, hemoglobin, MCH and MCHC were lower as compared with controls (see Table 1). Eight controls and nine obese patients presented anemia (hemoglobin b12 g/dL in women and b 13 g/dL in men). When these subjects were excluded from the analysis, the same
Table 1 Inflammatory and hematological parameters in case and control subjects.
Sex (f/m) Age (years) BMI (kg/m2) RDW (%) CRP (mg/L) Fibrinogen (mg/dL) Leukocytes (103/μL) Neutrophils (103/μL) Hemoglobin (g/dL) Fe (μg/dL) MCV (fL) MCH (pg) MCHC (g/dL)
Case (n = 142)
Control (n = 144)
p-Value
101/41 43.45 ± 11.99 46.10 ± 6.40 14.19 ± 1.23 7.11 (0.24–40.30) 383 (253–681) 7.71 ± 2.20 4.55 ± 1.70 13.70 ± 1.27 73.53 ± 27.74 87.75 ± 5.79 28.92 ± 2.33 33.04 ± 1.44
94/50 44.19 ± 13.24 24.33 ± 3.25 13.24 ± 0.80 0.96 (0.16–27.05) 309 (212–535) 6.17 ± 1.47 3.50 ± 1.16 14.03 ± 1.14 92.44 ± 30.80 87.97 ± 4.18 29.68 ± 1.67 33.73 ± 1.02
0.375a 0.634 b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 0.026 b0.001 0.729 0.002 b0.001
BMI: body mass index, RDW: red blood distribution width, CRP: C-reactive protein, MCV: mean corpuscular volume, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration. a Chi-square test.
differences between controls and patients were found (data not shown). In morbidly obese patients, RDW correlated inversely with hemoglobin, serum iron, MCV, MCH, and MCHC (p b 0.001 all) but not with inflammatory parameters (p N 0.05). Univariate and multivariate logistic regression analyses were conducted to identify the independent variables as predictors of RDW N 14% (Table 2). While the univariate analysis showed that hemoglobin b 12.88 g/dL, iron b 62 μg/dL, MCV b 83.78 fL and MCH b 28.24 pg increased the risk of high RDW, the multivariate adjustment revealed that only low serum iron and MCH levels were associated with RDW N 14% (OR 7.61, 95% CI: 1.93–30.05, p = 0.004; OR 5.67, 95% CI: 1.98–16.24, p = 0.001; respectively).
Discussion This study, carried on a large group of patients (n = 142) and normal-weight subjects (n = 144), is the first to explore the association of RDW with morbid obesity. The results show that RDW is higher in morbidly obese patients as compared to controls (Table 1). Fujita et al. [7] conducted a study in adolescents and observed that RDW was higher in overweight vs. normal-weight subjects, which is in agreement with our results, although he observed an association between RDW and inflammatory parameters. However, the correlation analysis done with our data indicates that RDW inversely correlated with erythrocyte indices and serum iron levels, but not with inflammatory parameters. Moreover, the logistic regression analysis show that only MCH b 28 pg and Fe b 62 μg/dL increase the risk of RDW N 14% in obese patients. Accordingly, the highest RDW tertile presents a marked decrease in erythrocyte indices and serum iron levels (data not shown). All these data suggest that elevated RDW in the morbidly obese may reflect a mild hypochromic RBC state that is not related to inflammatory status, but to dietary deficiencies. In fact, as a previous treatment to bariatric surgery, patients were on a very low-calorie diet (Optifast®, 600 kcal, 52 g protein, 45 g carbohydrates and 7 g fat, 3 times a day for 6 weeks) without vitamin complements. Thus it is conceivable that the lower serum iron and, consequently, hypochromic erythrocyte are observed in the morbidly obese. In line with this hypothesis, Fujita et al. [7] did not find elevated RDW in overweight mice, but observed increased RDW in mice after following a high-calorie diet and having switched to a normalcalorie diet. The association of inflammation with increased RDW has been suggested in several conditions via cytokine-erythrocyte maturation [4]. In the present study, we failed to find an association between inflammatory parameters and RDW, which contrasts with Fujita et al. [7]. Nevertheless, it should be pointed out that these authors did not determine erythrocyte indices (i.e., MCV, MCH, and MCHC). Moreover, obese children often present dietary deficiencies [10]. Therefore, these variables should have been considered in the correlation and lineal regression analyses performed by these authors.
466
A. Vayá et al. / Clinical Biochemistry 47 (2014) 464–466
Conclusions In summary, the results of the present study indicate that RDW should not be considered an inflammatory marker in morbidly obese patients as it is not related to inflammatory status, but to hyposideremia, and, consequently, to lower erythrocyte indices. Conflict of interest All authors state no competing financial interests. Acknowledgments We thank Ms. Carmen Monter for her excellent technical assistance and Mrs. Alicia Ricart for her help into English translation. References [1] Lee WS, Kim TY. Relation between red blood cell distribution width and inflammatory biomarkers in rheumatoid arthritis. Arch Pathol Lab Med 2010;134:505–6.
[2] Lippi G, Filippozzi L, Montagnana M, Salvagno GL, Franchini M, Guidi GC, et al. Clinical usefulness of measuring red blood cell distribution width on admission in patients with acute coronary syndromes. Clin Chem Lab Med 2009;47: 353–7. [3] Ku NS, Kim HW, Oh HJ, Kim YC, Kim MH, Song JE, et al. Red blood cell distribution width is an independent predictor of mortality in patients with gram-negative bacteremia. Shock 2012;38:123–7. [4] Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352: 1011–23. [5] Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006;17:4–12. [6] Zeyda M, Stulnig TM. Obesity, inflammation, and insulin resistance — a mini-review. Gerontology 2009;55:379–86. [7] Fujita B, Strodthoff D, Fritzenwanger M, Pfeil A, Ferrari M, Goebel B, et al. Altered red blood cell distribution width in overweight adolescents and its association with markers of inflammation. Pediatr Obes 2013;8:385–91. [8] Lippi G, Sanchis-Gomar F, Danese E, Montagnana M. Association of red blood cell distribution width with plasma lipids in a general population of unselected outpatients. Kardiol Pol 2013;71:931–6. [9] Vayá A, Hernández-Mijares A, Suescun M, Solá E, Cámara R, Romagnoli M, et al. Metabolic alterations in morbid obesity. Influence on the haemorheological profile. Clin Hemorheol Microcirc 2011;48:247–55. [10] Pinhas-Hamiel O, Doron-Panush N, Reichman B, Nitzan-Kaluski D, Shalitin S, Geva-Lerner L. Obese children and adolescents: a risk group for low vitamin b12 concentration. Arch Pediatr Adolesc Med 2006;160:933–6.
Contents lists available at ScienceDirect
Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem
Short Communication
Red blood cell distribution width is not related with inflammatory parameters in morbidly obese patients Amparo Vayá a,⁎, Rafael Alis b,c, Antonio Hernandez-Mijares d, Eva Solá d, Rosa Cámara e, Leonor Rivera a, Marco Romagnoli b,f, Begoña Laiz a a
Hemorheology and Haemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Valencia, Spain Universitary Research Institute “Dr. Viña Giner”, Molecular and Mitochondrial Medicine, Catholic University of Valencia “San Vicente Mártir”, Valencia, Spain Faculty of Medicine, Catholic University of Valencia "San Vicente Mártir", Valencia, Spain d Endocrinology Service, Dr. Peset University Hospital, Valencia, Spain e Endocrinology Service, La Fe University Hospital, Valencia, Spain f Department of Physical Education and Sports, Catholic University of Valencia "San Vicente Mártir", Valencia, Spain. b c
a r t i c l e
i n f o
Article history: Received 10 October 2013 Received in revised form 27 December 2013 Accepted 17 January 2014 Available online 1 February 2014 Keywords: Obesity Inflammation Red blood distribution width Anemia
a b s t r a c t Objective: Red blood cell distribution width (RDW) is a hematological parameter that has been studied in several clinical settings and has been found to be related to both anemia and inflammatory status. As obesity is related to increased inflammatory pattern, we aimed to analyze the RDW in this setting. Methods: We determined hematological and inflammatory parameters in morbidly obese patients before bariatric surgery (n = 142) and normo-weight controls (n = 144). Results: RDW was higher in patients than in controls (p b 0.001), along with C-reactive protein (p b 0.001) and fibrinogen, (p b 0.001) while hemoglobin (p = 0.026), serum iron (p b 0.001), MCH (p = 0.002) and MCHC (p b 0.001) were lower in morbidly obese patients. The logistic correlation analysis revealed that only low serum iron (b62 μg/dL) and MCH (b 28.14 pg) levels were associated with RDW N 14% (OR 7.61, 95% CI: 1.93–30.04, p = 0.004; OR 5.67, 95% CI: 1.98–16.24, p = 0.001; respectively). Conclusions: These data indicate that the elevated RDW in morbidly obese patients reflects a mild red blood cell hypochromia that does not relate to inflammatory parameters, but to hyposideremia and, consequently, to lower erythrocyte indices, possibly as a result of being on a very low-calorie diet before bariatric surgery. Therefore, RDW should not be considered as an inflammatory marker in this clinical setting. Crown Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
Introduction The association of red blood distribution width (RDW) with several clinical settings has been thoroughly explored in recent years. High RDW has been linked with autoimmune diseases [1], cardiovascular events [2] or infectious processes [3]. It has also been shown that the activity of pro-inflammatory cytokines causes a dysregulation of iron homeostasis, inhibits the proliferation of erythroid progenitor cells and impairs the erythropoietin-gene expression [4], leading to increased RDW. As obese patients present an elevated inflammatory status [5,6], it may be an interesting clinical setting to explore the association of RDW with inflammatory parameters. In fact, a recent study reported that obese adolescents show elevated RDW and, no overweight, but nutritional changes cause elevated RDW in an animal model [7]. Moreover, it has been shown that higher RDW is associated with a globally unfavorable lipid profile [8]. To further investigate this issue, we aimed to
⁎ Corresponding author at: Hemorheology and Hemostasis Unit, Service of Clinical Pathology, La Fe University Hospital, Avda. de Campanar, 21, 46009 Valencia, Spain. Fax: +34 963862714. E-mail address: [email protected] (A. Vayá).
study RDW values along with hematological and inflammatory parameters in morbidly obese patients before bariatric surgery. Material and methods Patients The patient group consisted of 142 morbidly (BMI N 40 kg/m2) obese patients (101 women, 41 men). Patients attended the Endocrinology Services at the La Fe and the Doctor Peset University Hospitals (Valencia, Spain) between 2009 and 2012. Some participated in the study published by our group in 2010 [9]. The control group comprised 144 healthy normal-weight (BMI b 30 kg/m2) volunteers (94 women, 50 men), consisting of non-consanguineous relatives or friends of patients, who were age- and sex-matched. The inclusion of patients and controls in the study was performed simultaneously, as sampling and analytical testing. Informed consent from all the participants and approval from La Fe University Hospital's Ethics Committee were obtained. This work complies with the principles of the Declaration of Helsinki. The exclusion criteria were organic, malignant, hematological, infectious or inflammatory disease, previous history of ischemic heart disease
0009-9120/$ – see front matter. Crown Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clinbiochem.2014.01.020
A. Vayá et al. / Clinical Biochemistry 47 (2014) 464–466
or stroke, previous thrombo-embolism, treatment with rheological drugs and secondary obesity (hypothyroidism, Cushing syndrome).
465
Table 2 Predictors for high RDW (≥14%). Crude
Laboratory methods Venous blood was drawn from the antecubital vein between 8 and 10 a.m. after 12 h of fasting with a minimum stasis. Basic hematological parameters were determined by a Sysmex XE-2100 (Roche Diagnostics S.L., Barcelona, Spain). Fibrinogen was performed in an ACL-TOP autoanalyzer (Instrumentation Laboratory, Milan, Italy) using coagulometric techniques. C-reactive protein (CRP) was determined by immunoturbidity and iron by colorimetry in an Olympus AU 5430 autoanalyzer.
CRP ≥ 5.73 (mg/L) Fibrinogen ≥ 369 (mg/dL) Leukocytes ≥ 7.64 (103/μL) Neutrophils ≥ 4.66 (103/μL) Hemoglobin b 12.88 (g/dL) Fe b 62 (μg/dL) MCV b 83.78 (fL) MCH b 28.24 (pg)
Adjusted
OR
95% CI
P
OR
95% CI
Pa
1.71 1.17 1.32 1.53 5.56 8.25 7.40 8.50
0.83–3.52 0.57–2.39 0.67–2.63 0.76 3.06 2.16–14.34 3.67–18.57 2.56–21.36 3.72–19.41
0.149 0.667 0.426 0.233 b0.001 b0.001 b0.001 b0.001
1.17 0.52 0.62 2.51 2.98 5.67 0.80 7.62
0.41–3.32 0.19–1.47 0.16–2.42 0.63 10.11 0.87–10.25 1.98–16.24 0.15–4.19 1.93–30.05
0.767 0.219 0.491 0.194 0.083 0.001 0.790 0.004
RDW: red blood distribution width, CRP: C-reactive protein, MCV: mean corpuscular volume, MCH: mean corpuscular hemoglobin. a Adjusted for all the others parameters.
Statistical analysis All the continuous variables were checked for normal distribution with the Kolmogorov–Smirnov test. CRP and fibrinogen were logtransformed to improve normality for statistical testing. A t-test for independent measures was used to compare the mean values in the continuous variables between obese patients and controls. Chi square tests were conducted to compare the percentages in dichotomic variables. Pearson' correlation coefficients were calculated to explore the crude relationship between continuous variables. When data were not normally distributed, correlation analyses were performed by Spearman's correlation coefficient (ρ). A logistic regression analysis was applied to estimate the unadjusted and multivariate-adjusted odds ratios (OR) and the 95% confidence intervals (CI) for independent variables on the risk for high RDW N 14%. The cut-off points for the dependent and independent variables were calculated from the mean values plus or minus one standard deviation (SD) of control subjects. Data are expressed as mean ± SD for normally distributed data and as median (min–max) for non-normally distributed data. P values of b0.05 were considered statistically significant. The statistical analysis was performed using SPSS version 15 (SPSS inc. Chicago, IL, USA). Results Table 1 summarizes the baseline characteristics of morbidly obese patients and control subjects. Inflammatory parameters (CRP, fibrinogen, leukocytes and neutrophils) were higher in patients, while serum iron, hemoglobin, MCH and MCHC were lower as compared with controls (see Table 1). Eight controls and nine obese patients presented anemia (hemoglobin b12 g/dL in women and b 13 g/dL in men). When these subjects were excluded from the analysis, the same
Table 1 Inflammatory and hematological parameters in case and control subjects.
Sex (f/m) Age (years) BMI (kg/m2) RDW (%) CRP (mg/L) Fibrinogen (mg/dL) Leukocytes (103/μL) Neutrophils (103/μL) Hemoglobin (g/dL) Fe (μg/dL) MCV (fL) MCH (pg) MCHC (g/dL)
Case (n = 142)
Control (n = 144)
p-Value
101/41 43.45 ± 11.99 46.10 ± 6.40 14.19 ± 1.23 7.11 (0.24–40.30) 383 (253–681) 7.71 ± 2.20 4.55 ± 1.70 13.70 ± 1.27 73.53 ± 27.74 87.75 ± 5.79 28.92 ± 2.33 33.04 ± 1.44
94/50 44.19 ± 13.24 24.33 ± 3.25 13.24 ± 0.80 0.96 (0.16–27.05) 309 (212–535) 6.17 ± 1.47 3.50 ± 1.16 14.03 ± 1.14 92.44 ± 30.80 87.97 ± 4.18 29.68 ± 1.67 33.73 ± 1.02
0.375a 0.634 b0.001 b0.001 b0.001 b0.001 b0.001 b0.001 0.026 b0.001 0.729 0.002 b0.001
BMI: body mass index, RDW: red blood distribution width, CRP: C-reactive protein, MCV: mean corpuscular volume, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration. a Chi-square test.
differences between controls and patients were found (data not shown). In morbidly obese patients, RDW correlated inversely with hemoglobin, serum iron, MCV, MCH, and MCHC (p b 0.001 all) but not with inflammatory parameters (p N 0.05). Univariate and multivariate logistic regression analyses were conducted to identify the independent variables as predictors of RDW N 14% (Table 2). While the univariate analysis showed that hemoglobin b 12.88 g/dL, iron b 62 μg/dL, MCV b 83.78 fL and MCH b 28.24 pg increased the risk of high RDW, the multivariate adjustment revealed that only low serum iron and MCH levels were associated with RDW N 14% (OR 7.61, 95% CI: 1.93–30.05, p = 0.004; OR 5.67, 95% CI: 1.98–16.24, p = 0.001; respectively).
Discussion This study, carried on a large group of patients (n = 142) and normal-weight subjects (n = 144), is the first to explore the association of RDW with morbid obesity. The results show that RDW is higher in morbidly obese patients as compared to controls (Table 1). Fujita et al. [7] conducted a study in adolescents and observed that RDW was higher in overweight vs. normal-weight subjects, which is in agreement with our results, although he observed an association between RDW and inflammatory parameters. However, the correlation analysis done with our data indicates that RDW inversely correlated with erythrocyte indices and serum iron levels, but not with inflammatory parameters. Moreover, the logistic regression analysis show that only MCH b 28 pg and Fe b 62 μg/dL increase the risk of RDW N 14% in obese patients. Accordingly, the highest RDW tertile presents a marked decrease in erythrocyte indices and serum iron levels (data not shown). All these data suggest that elevated RDW in the morbidly obese may reflect a mild hypochromic RBC state that is not related to inflammatory status, but to dietary deficiencies. In fact, as a previous treatment to bariatric surgery, patients were on a very low-calorie diet (Optifast®, 600 kcal, 52 g protein, 45 g carbohydrates and 7 g fat, 3 times a day for 6 weeks) without vitamin complements. Thus it is conceivable that the lower serum iron and, consequently, hypochromic erythrocyte are observed in the morbidly obese. In line with this hypothesis, Fujita et al. [7] did not find elevated RDW in overweight mice, but observed increased RDW in mice after following a high-calorie diet and having switched to a normalcalorie diet. The association of inflammation with increased RDW has been suggested in several conditions via cytokine-erythrocyte maturation [4]. In the present study, we failed to find an association between inflammatory parameters and RDW, which contrasts with Fujita et al. [7]. Nevertheless, it should be pointed out that these authors did not determine erythrocyte indices (i.e., MCV, MCH, and MCHC). Moreover, obese children often present dietary deficiencies [10]. Therefore, these variables should have been considered in the correlation and lineal regression analyses performed by these authors.
466
A. Vayá et al. / Clinical Biochemistry 47 (2014) 464–466
Conclusions In summary, the results of the present study indicate that RDW should not be considered an inflammatory marker in morbidly obese patients as it is not related to inflammatory status, but to hyposideremia, and, consequently, to lower erythrocyte indices. Conflict of interest All authors state no competing financial interests. Acknowledgments We thank Ms. Carmen Monter for her excellent technical assistance and Mrs. Alicia Ricart for her help into English translation. References [1] Lee WS, Kim TY. Relation between red blood cell distribution width and inflammatory biomarkers in rheumatoid arthritis. Arch Pathol Lab Med 2010;134:505–6.
[2] Lippi G, Filippozzi L, Montagnana M, Salvagno GL, Franchini M, Guidi GC, et al. Clinical usefulness of measuring red blood cell distribution width on admission in patients with acute coronary syndromes. Clin Chem Lab Med 2009;47: 353–7. [3] Ku NS, Kim HW, Oh HJ, Kim YC, Kim MH, Song JE, et al. Red blood cell distribution width is an independent predictor of mortality in patients with gram-negative bacteremia. Shock 2012;38:123–7. [4] Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med 2005;352: 1011–23. [5] Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 2006;17:4–12. [6] Zeyda M, Stulnig TM. Obesity, inflammation, and insulin resistance — a mini-review. Gerontology 2009;55:379–86. [7] Fujita B, Strodthoff D, Fritzenwanger M, Pfeil A, Ferrari M, Goebel B, et al. Altered red blood cell distribution width in overweight adolescents and its association with markers of inflammation. Pediatr Obes 2013;8:385–91. [8] Lippi G, Sanchis-Gomar F, Danese E, Montagnana M. Association of red blood cell distribution width with plasma lipids in a general population of unselected outpatients. Kardiol Pol 2013;71:931–6. [9] Vayá A, Hernández-Mijares A, Suescun M, Solá E, Cámara R, Romagnoli M, et al. Metabolic alterations in morbid obesity. Influence on the haemorheological profile. Clin Hemorheol Microcirc 2011;48:247–55. [10] Pinhas-Hamiel O, Doron-Panush N, Reichman B, Nitzan-Kaluski D, Shalitin S, Geva-Lerner L. Obese children and adolescents: a risk group for low vitamin b12 concentration. Arch Pediatr Adolesc Med 2006;160:933–6.