International Journal of Cardiology 176 (2014) 1379–1381
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
An increasing of red blood cell distribution width was associated with cardiovascular mortality in patients on peritoneal dialysis Fenfen Peng 1, Zhijian Li 1, Zhong Zhong, Qimei Luo, Qunying Guo, Fengxian Huang, Xueqing Yu, Xiao Yang ⁎ Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Nephrology, Ministry of Health, Guangzhou 510080, China
a r t i c l e
i n f o
Article history: Received 31 July 2014 Accepted 2 August 2014 Available online 11 August 2014 Keywords: Red blood cell distribution width Cardiovascular disease Mortality Peritoneal dialysis
Peritoneal dialysis (PD) has been widely accepted for the treatment in patients with end stage renal disease (ERSD). Cardiovascular disease (CVD) is the leading cause of death in these patients, accounting for 40%–50% of all-cause mortality [1]. Anemia, prevalent in PD patients, is one of the risk factors that strongly predict CVD mortality in this dialysis population [2]. Red blood cell distribution width (RDW) is an index of erythrocyte volume variability (anisocytosis) and routinely reported as a part of a complete blood cell count [3]. As a substrate for ineffective erythropoiesis (such as iron deficiency, folate or B12 deficiency, and hemoglobinopathies) [4], RDW is usually used together with mean corpuscular volume (MCV) to differentiate the cause of anemia [3]. Recently, it was observed that high RDW levels were also associated with an increased risk of adverse outcomes in general population [5], severe sepsis [6], and population referred for coronary angiography [7]. However, direct clinical evidence for the association of RDW and outcomes of PD patients is lacking. In this retrospective observational cohort study, we try to test the hypothesis that higher values of RDW may be independently associated with the risk of CVD mortality in PD patients. Patients were recruited from the PD center at The First Affiliated Hospital, Sun Yat-sen University, from January 1, 2006 to December 31, 2011. The inclusion criteria were all incident patients ≥ 18 years old, the PD catheter insertion performed in our center and patients ⁎ Corresponding author at: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou 510080, China. Tel.: +86 20 87766335; fax: +86 20 87769673. E-mail address: [email protected] (X. Yang). 1 Fenfen Peng and Zhijian Li contributed equally to this study.
http://dx.doi.org/10.1016/j.ijcard.2014.08.030 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
who received PD therapy more than 90 days. Patients referred from other PD centers, transferred from permanent hemodialysis or failed renal transplantation, or had a history of malignant disease or no RDW information were excluded. The study was conducted in compliance with the ethical principles of the Helsinki Declaration (http://www. wma.net/en/30publications/10policies/b3/index.html) and approved by the Human Ethics Committees of Sun Yat-sen University. Written informed consent was obtained from all participants. Baseline demographic, clinical and laboratory data were obtained during the first 1–3 months of PD. Residual kidney function and total Kt/V were calculated using PD Adequest software 2.0 (Baxter Healthcare Ltd.). The primary outcomes of this study were all-cause mortality and CVD mortality. CVD mortality was defined as death due to acute myocardial infarction, atherosclerotic heart disease, cardiomyopathy, cardiac arrhythmia, cardiac arrest, congestive heart failure, intracranial hemorrhage, cerebral infarction, and peripheral vascular disease [1]. All patients were followed up until cessation of PD, death or on December 31, 2013. According to RDW normal reference in our hospital, patients with measured RDW values were divided into two groups: RDW b 15.5% and RDW ≥ 15.5% (the upper limit of normal). Survival curves were estimated from Kaplan–Meier analysis. The associations of RDW levels with all-cause and CVD mortality were assessed using multivariable-adjusted Cox models. All calculations were performed using SPSS, version 17.0 for Windows (SPSS Inc.). P values b 0.05 were considered to be statistically significant. A total of 1293 eligible incident PD patients were enrolled in this study (mean age: 49.4 ± 15.3 years, 58.9% were male), with a median follow-up of 34.3 months (range: 3–95.7). Baseline demographic and clinical characteristics of the cohort study categorized according to RDW value are given in Table 1. Patients with RDW ≥ 15.5% had a higher rate of CVD and diabetes, higher levels of Charlson comorbidity index (CCI), neutrophil to lymphocyte ratio (N/L), and high sensitive C-reactive protein (Hs-CRP), but a lower body mass index (BMI), diastolic blood pressure, hemoglobin, hematocrit, serum albumin, prealbumin, transferrin and 24 h urine output. In the correlation analysis, RDW levels positively correlated with CCI and Hs-CRP and negatively correlated with hemoglobin, hematocrit, albumin, prealbumin, and transferrin (P b 0.01) (Supplement Table 1). During follow-up period, 107 (8.3%) patients were transferred to hemodialysis, 216 (16.7%) patients underwent renal transplantation, 59 (4.6%) patients transferred to other centers, 40 (3.1%) patients were lost to follow-up, 9 (0.7%) patients declined to further treatment
1380
F. Peng et al. / International Journal of Cardiology 176 (2014) 1379–1381
Table 1 Baseline characteristics of PD patients by RDW value. RDW b 15.5% n = 1017
RDW ≥ 15.5% n = 276
P value
Demographics Gender (man, n, %) Age (y) Body mass index (kg/m2)
609 (59.9%) 46.9 ± 14.9 21.5 ± 3.0
152 (55.1%) 51.5 ± 15.8 21.1 ± 3.2
0.150 b0.001 0.050
Comorbid conditions Cardiovascular disease (n, %) Diabetes mellitus (n, %) Hypertension (n, %) Systolic BP (mm Hg) Diastolic BP (mm Hg) Charlson comorbidity index
363 (35.7%) 242 (23.8%) 655 (64.4%) 135.8 ± 20.0 85.1 ± 14.7 3.5 ± 1.8
125 (45.3%) 81 (29.3%) 173 (62.7%) 135.6 ± 21.2 82.2 ± 14.6 4.2 ± 2.1
0.004 0.059 0.597 0.559 0.005 b0.001
Laboratory variables N/L Hemoglobin (g/dL) Hematocrit (%) Serum albumin (g/dL) Prealbumin (mg/dL) Transferrin (g/dL) Albumin-corrected calcium (mmol/L) Serum phosphorus (mmol/L) Total cholesterol (mmol/L) Total triglycerides (mmol/L) hs-CRP (mg/L) Total Kt/V 24 h urine output (mL) RKF (mL/min/1.73 m2) Serum uric acid (μmol/L) Serum urea nitrogen (mmol/L) Serum creatinine (μmol/L)
2.8 [1.6] 10.5 ± 2.0 31.8 ± 6.6 3.8 ± 0.5 34.9 ± 10.1 0.22 [0.07] 2.46 ± 0.35 1.47 ± 0.48 5.08 ± 1.27 1.70 ± 1.23 1.69 [5.16] 2.4 ± 0.7 809 ± 518 3.7 ± 2.8 421 ± 92 15.8 [7.2] 768 ± 281
2.8 [2.0] 9.4 ± 2.2 29.9 ± 7.0 3.6 ± 0.5 33.4 ± 11.3 0.20 [0.08] 2.46 ± 0.22 1.49 ± 0.55 5.11 ± 1.47 1.78 ± 1.88 2.2 [9.67] 2.3 ± 0.6 728 ± 498 3.4 ± 2.5 426 ± 102 15.8 [7.5] 735 ± 295
b0.001 b0.001 b0.001 b0.001 0.04 0.001 0.81 0.54 0.77 0.41 0.001 0.067 0.025 0.095 0.59 0.33 0.09
Treatment Erythropoietin Chalybeatus Folic acid
793 (78%) 564 (55.5%) 554 (54.5%)
203 (73.6%) 139 (50.4%) 132 (47.8%)
0.121 0.132 0.050
Variables
Values for continuous variables are given as mean ± standard deviation or median [interquartile range]. BP, blood pressure; hs-CRP, high-sensitivity C-reactive protein; NA, not applicable; N/L, neutrophil to lymphocyte ratio; RKF, residual kidney function.
and the remaining 613 (47.4%) patients were still followed-up at our PD center. A total of 249 deaths (19.3%) were recorded, among which 132 (53%) were caused by CVD. Kaplan–Meier analysis showed that the all-cause and CVD mortality were significantly higher in the patients
with RDW ≥ 15.5% (Fig. 1). The associations of RDW level with allcause and CVD mortality with defined models are listed in Table 2. After adjusting for age, sex, CCI, blood pressure, 24 h urine output, N/L, serum albumin, serum urea nitrogen and triglycerides, and anemia parameters including hemoglobin, use of erythropoietin, chalybeatus and folic acid, the patients with RDW ≥ 15.5% had a hazard ratio of 1.60 (95% CI: 1.08–2.39, P = 0.021) for CVD mortality. However, there was no significant association between higher levels of RDW and allcause mortality (P = 0.132). CVD is the leading cause of death in hemodialysis and PD patients [1]. It is well known that anemia is prevalent in ESRD patients that is due to a reduction in erythropoietin production, inflammation, shortening of red-cell survival as well as iron or folate deficiency and contributes to the higher mortality in patients with dialysis [2]. RDW value is an index of erythrocyte volume variability (anisocytosis) and its variability may reflect the anemia. In our study, hemoglobin level and hematocrit value significantly lower in patients with RDW ≥ 15.5%, and negatively correlated with RDW. However, the association between RDW and CVD mortality persisted after adjusting for hemoglobin and anemia treatment agents, which suggests that the relationship between RDW and CVD mortality may be independent of anemia. Recently, RDW levels have been demonstrated to be a data reflecting malnutrition and inflammation [4], which have been well documented with an increased risk of CVD mortality in dialysis patients [8,9]. In this study, we found that RDW was negatively correlated with malnutrition parameters (albumin, prealbumin, and transferrin) and positively with hs-CRP levels, providing evidence that poor nutrition and increased inflammation may involve the increasing RDW levels in PD patients. In addition, high RDW is associated with decreased red blood cell deformability, which can impair blood flow through the microcirculation [10]. The resultant hypoxia may help to explain increased risk of CVD mortality in patients with high RDW. Taken together, RDW may act as an integrate factor of malnutrition, inflammation, anemia, and hypoxia, thereby contributing to the higher CVD mortality in PD patients. Future studies need to determine the potential mechanism of RDW in ESRD patients. In conclusion, it was firstly found that higher RDW was independently associated with the increased CVD-mortality in PD patients. These findings suggest that high RDW may be a potential predictor of CVD morality in PD patients.
Fig. 1. Crude analyses of all-cause and cardiovascular mortality between RDW groups. Kaplan–Meier estimates of (A) all-cause and (B) cardiovascular mortality.
F. Peng et al. / International Journal of Cardiology 176 (2014) 1379–1381 Table 2 Association between RDW and all-cause and cardiovascular mortality.
Unadjusted RDW ≥ 15.5% (vs) RDW b 15.5% Model 1a RDW ≥ 15.5% (vs) RDW b 15.5% Model 2b RDW ≥ 15.5% (vs) RDW b 15.5%
All-cause mortality
CVD mortality
1.68 (1.28, 2.22), b0.001
2.15 (1.50, 3.09), b0.001
1.41 (1.04, 1.90), 0.029
1.83 (1.24, 2.70), 0.002
1.27 (0.93, 1.75), 0.132
1.60 (1.08, 2.39), 0.021
1381
Acknowledgments The authors thank Jianxiong Lin, Chunyan Yi, Xinhui Liu, Xi Xia, Richong Xu, and Chen Zhao for their assistance in data collection; all nephrologists and nurses in our PD center for their excellent management of PD patients; and Fenghua Xu and Qian Zhou for their assistance in statistical analyses. References
CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; RDW, red blood cell distribution width. a Adjusted for age, gender, diastolic blood pressure, Charlson comorbidity index, 24 h urine output divided by 100, N/L, serum albumin, triglyceride, serum urea nitrogen. b Adjusted for model 1 covariates and hemoglobin and use of erythropoietin, chalybeatus and folic acid.
Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ijcard.2014.08.030. Funding source This work was supported by the Key Clinical Program of the Ministry of Health, China (2010-439), Guangdong Natural Science Foundation of China (9151008901000051, S2011010005077, and S2013010016002), National Basic Research Program of China (Grant No. 2011CB504000) and Guangzhou Committee of Science and Technology, China (Grant No. 2010U1-E00831). Conflict of interest The authors stated that there are no conflicts of interest.
[1] Liu X, Guo Q, Feng X, et al. Alkaline phosphatase and mortality in patients on peritoneal dialysis. Clin J Am Soc Nephrol 2014;9:771–8. [2] Molnar MZ, Mehrotra R, Duong U, Kovesdy CP, Kalantar-Zadeh K. Association of hemoglobin and survival in peritoneal dialysis patients. Clin J Am Soc Nephrol 2011;6: 1973–81. [3] Karnad A, Poskitt TR. The automated complete blood cell count. Use of the red blood cell volume distribution width and mean platelet volume in evaluating anemia and thrombocytopenia. Arch Intern Med 1985;145:1270–2. [4] Forhecz Z, Gombos T, Borgulya G, Pozsonyi Z, Prohaszka Z, Janoskuti L. Red cell distribution width in heart failure: prediction of clinical events and relationship with markers of ineffective erythropoiesis, inflammation, renal function, and nutritional state. Am Heart J 2009;158:659–66. [5] Perlstein TS, Weuve J, Pfeffer MA, Beckman JA. Red blood cell distribution width and mortality risk in a community-based prospective cohort. Arch Intern Med 2009;169: 588–94. [6] Kim CH, Park JT, Kim EJ, et al. An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. Crit Care 2013;17:R282. [7] Cavusoglu E, Chopra V, Gupta A, et al. Relation between red blood cell distribution width (RDW) and all-cause mortality at two years in an unselected population referred for coronary angiography. Int J Cardiol 2010;141:141–6. [8] Lambie M, Chess J, Donovan KL, et al. Independent effects of systemic and peritoneal inflammation on peritoneal dialysis survival. J Am Soc Nephrol 2013;24:2071–80. [9] Peev V, Nayer A, Contreras G. Dyslipidemia, malnutrition, inflammation, cardiovascular disease and mortality in chronic kidney disease. Curr Opin Lipidol 2014;25: 54–60. [10] Patel KV, Mohanty JG, Kanapuru B, Hesdorffer C, Ershler WB, Rifkind JM. Association of the red cell distribution width with red blood cell deformability. Adv Exp Med Biol 2013;765:211–6.
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
An increasing of red blood cell distribution width was associated with cardiovascular mortality in patients on peritoneal dialysis Fenfen Peng 1, Zhijian Li 1, Zhong Zhong, Qimei Luo, Qunying Guo, Fengxian Huang, Xueqing Yu, Xiao Yang ⁎ Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China Key Laboratory of Nephrology, Ministry of Health, Guangzhou 510080, China
a r t i c l e
i n f o
Article history: Received 31 July 2014 Accepted 2 August 2014 Available online 11 August 2014 Keywords: Red blood cell distribution width Cardiovascular disease Mortality Peritoneal dialysis
Peritoneal dialysis (PD) has been widely accepted for the treatment in patients with end stage renal disease (ERSD). Cardiovascular disease (CVD) is the leading cause of death in these patients, accounting for 40%–50% of all-cause mortality [1]. Anemia, prevalent in PD patients, is one of the risk factors that strongly predict CVD mortality in this dialysis population [2]. Red blood cell distribution width (RDW) is an index of erythrocyte volume variability (anisocytosis) and routinely reported as a part of a complete blood cell count [3]. As a substrate for ineffective erythropoiesis (such as iron deficiency, folate or B12 deficiency, and hemoglobinopathies) [4], RDW is usually used together with mean corpuscular volume (MCV) to differentiate the cause of anemia [3]. Recently, it was observed that high RDW levels were also associated with an increased risk of adverse outcomes in general population [5], severe sepsis [6], and population referred for coronary angiography [7]. However, direct clinical evidence for the association of RDW and outcomes of PD patients is lacking. In this retrospective observational cohort study, we try to test the hypothesis that higher values of RDW may be independently associated with the risk of CVD mortality in PD patients. Patients were recruited from the PD center at The First Affiliated Hospital, Sun Yat-sen University, from January 1, 2006 to December 31, 2011. The inclusion criteria were all incident patients ≥ 18 years old, the PD catheter insertion performed in our center and patients ⁎ Corresponding author at: Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, 58th, Zhongshan Road II, Guangzhou 510080, China. Tel.: +86 20 87766335; fax: +86 20 87769673. E-mail address: [email protected] (X. Yang). 1 Fenfen Peng and Zhijian Li contributed equally to this study.
http://dx.doi.org/10.1016/j.ijcard.2014.08.030 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
who received PD therapy more than 90 days. Patients referred from other PD centers, transferred from permanent hemodialysis or failed renal transplantation, or had a history of malignant disease or no RDW information were excluded. The study was conducted in compliance with the ethical principles of the Helsinki Declaration (http://www. wma.net/en/30publications/10policies/b3/index.html) and approved by the Human Ethics Committees of Sun Yat-sen University. Written informed consent was obtained from all participants. Baseline demographic, clinical and laboratory data were obtained during the first 1–3 months of PD. Residual kidney function and total Kt/V were calculated using PD Adequest software 2.0 (Baxter Healthcare Ltd.). The primary outcomes of this study were all-cause mortality and CVD mortality. CVD mortality was defined as death due to acute myocardial infarction, atherosclerotic heart disease, cardiomyopathy, cardiac arrhythmia, cardiac arrest, congestive heart failure, intracranial hemorrhage, cerebral infarction, and peripheral vascular disease [1]. All patients were followed up until cessation of PD, death or on December 31, 2013. According to RDW normal reference in our hospital, patients with measured RDW values were divided into two groups: RDW b 15.5% and RDW ≥ 15.5% (the upper limit of normal). Survival curves were estimated from Kaplan–Meier analysis. The associations of RDW levels with all-cause and CVD mortality were assessed using multivariable-adjusted Cox models. All calculations were performed using SPSS, version 17.0 for Windows (SPSS Inc.). P values b 0.05 were considered to be statistically significant. A total of 1293 eligible incident PD patients were enrolled in this study (mean age: 49.4 ± 15.3 years, 58.9% were male), with a median follow-up of 34.3 months (range: 3–95.7). Baseline demographic and clinical characteristics of the cohort study categorized according to RDW value are given in Table 1. Patients with RDW ≥ 15.5% had a higher rate of CVD and diabetes, higher levels of Charlson comorbidity index (CCI), neutrophil to lymphocyte ratio (N/L), and high sensitive C-reactive protein (Hs-CRP), but a lower body mass index (BMI), diastolic blood pressure, hemoglobin, hematocrit, serum albumin, prealbumin, transferrin and 24 h urine output. In the correlation analysis, RDW levels positively correlated with CCI and Hs-CRP and negatively correlated with hemoglobin, hematocrit, albumin, prealbumin, and transferrin (P b 0.01) (Supplement Table 1). During follow-up period, 107 (8.3%) patients were transferred to hemodialysis, 216 (16.7%) patients underwent renal transplantation, 59 (4.6%) patients transferred to other centers, 40 (3.1%) patients were lost to follow-up, 9 (0.7%) patients declined to further treatment
1380
F. Peng et al. / International Journal of Cardiology 176 (2014) 1379–1381
Table 1 Baseline characteristics of PD patients by RDW value. RDW b 15.5% n = 1017
RDW ≥ 15.5% n = 276
P value
Demographics Gender (man, n, %) Age (y) Body mass index (kg/m2)
609 (59.9%) 46.9 ± 14.9 21.5 ± 3.0
152 (55.1%) 51.5 ± 15.8 21.1 ± 3.2
0.150 b0.001 0.050
Comorbid conditions Cardiovascular disease (n, %) Diabetes mellitus (n, %) Hypertension (n, %) Systolic BP (mm Hg) Diastolic BP (mm Hg) Charlson comorbidity index
363 (35.7%) 242 (23.8%) 655 (64.4%) 135.8 ± 20.0 85.1 ± 14.7 3.5 ± 1.8
125 (45.3%) 81 (29.3%) 173 (62.7%) 135.6 ± 21.2 82.2 ± 14.6 4.2 ± 2.1
0.004 0.059 0.597 0.559 0.005 b0.001
Laboratory variables N/L Hemoglobin (g/dL) Hematocrit (%) Serum albumin (g/dL) Prealbumin (mg/dL) Transferrin (g/dL) Albumin-corrected calcium (mmol/L) Serum phosphorus (mmol/L) Total cholesterol (mmol/L) Total triglycerides (mmol/L) hs-CRP (mg/L) Total Kt/V 24 h urine output (mL) RKF (mL/min/1.73 m2) Serum uric acid (μmol/L) Serum urea nitrogen (mmol/L) Serum creatinine (μmol/L)
2.8 [1.6] 10.5 ± 2.0 31.8 ± 6.6 3.8 ± 0.5 34.9 ± 10.1 0.22 [0.07] 2.46 ± 0.35 1.47 ± 0.48 5.08 ± 1.27 1.70 ± 1.23 1.69 [5.16] 2.4 ± 0.7 809 ± 518 3.7 ± 2.8 421 ± 92 15.8 [7.2] 768 ± 281
2.8 [2.0] 9.4 ± 2.2 29.9 ± 7.0 3.6 ± 0.5 33.4 ± 11.3 0.20 [0.08] 2.46 ± 0.22 1.49 ± 0.55 5.11 ± 1.47 1.78 ± 1.88 2.2 [9.67] 2.3 ± 0.6 728 ± 498 3.4 ± 2.5 426 ± 102 15.8 [7.5] 735 ± 295
b0.001 b0.001 b0.001 b0.001 0.04 0.001 0.81 0.54 0.77 0.41 0.001 0.067 0.025 0.095 0.59 0.33 0.09
Treatment Erythropoietin Chalybeatus Folic acid
793 (78%) 564 (55.5%) 554 (54.5%)
203 (73.6%) 139 (50.4%) 132 (47.8%)
0.121 0.132 0.050
Variables
Values for continuous variables are given as mean ± standard deviation or median [interquartile range]. BP, blood pressure; hs-CRP, high-sensitivity C-reactive protein; NA, not applicable; N/L, neutrophil to lymphocyte ratio; RKF, residual kidney function.
and the remaining 613 (47.4%) patients were still followed-up at our PD center. A total of 249 deaths (19.3%) were recorded, among which 132 (53%) were caused by CVD. Kaplan–Meier analysis showed that the all-cause and CVD mortality were significantly higher in the patients
with RDW ≥ 15.5% (Fig. 1). The associations of RDW level with allcause and CVD mortality with defined models are listed in Table 2. After adjusting for age, sex, CCI, blood pressure, 24 h urine output, N/L, serum albumin, serum urea nitrogen and triglycerides, and anemia parameters including hemoglobin, use of erythropoietin, chalybeatus and folic acid, the patients with RDW ≥ 15.5% had a hazard ratio of 1.60 (95% CI: 1.08–2.39, P = 0.021) for CVD mortality. However, there was no significant association between higher levels of RDW and allcause mortality (P = 0.132). CVD is the leading cause of death in hemodialysis and PD patients [1]. It is well known that anemia is prevalent in ESRD patients that is due to a reduction in erythropoietin production, inflammation, shortening of red-cell survival as well as iron or folate deficiency and contributes to the higher mortality in patients with dialysis [2]. RDW value is an index of erythrocyte volume variability (anisocytosis) and its variability may reflect the anemia. In our study, hemoglobin level and hematocrit value significantly lower in patients with RDW ≥ 15.5%, and negatively correlated with RDW. However, the association between RDW and CVD mortality persisted after adjusting for hemoglobin and anemia treatment agents, which suggests that the relationship between RDW and CVD mortality may be independent of anemia. Recently, RDW levels have been demonstrated to be a data reflecting malnutrition and inflammation [4], which have been well documented with an increased risk of CVD mortality in dialysis patients [8,9]. In this study, we found that RDW was negatively correlated with malnutrition parameters (albumin, prealbumin, and transferrin) and positively with hs-CRP levels, providing evidence that poor nutrition and increased inflammation may involve the increasing RDW levels in PD patients. In addition, high RDW is associated with decreased red blood cell deformability, which can impair blood flow through the microcirculation [10]. The resultant hypoxia may help to explain increased risk of CVD mortality in patients with high RDW. Taken together, RDW may act as an integrate factor of malnutrition, inflammation, anemia, and hypoxia, thereby contributing to the higher CVD mortality in PD patients. Future studies need to determine the potential mechanism of RDW in ESRD patients. In conclusion, it was firstly found that higher RDW was independently associated with the increased CVD-mortality in PD patients. These findings suggest that high RDW may be a potential predictor of CVD morality in PD patients.
Fig. 1. Crude analyses of all-cause and cardiovascular mortality between RDW groups. Kaplan–Meier estimates of (A) all-cause and (B) cardiovascular mortality.
F. Peng et al. / International Journal of Cardiology 176 (2014) 1379–1381 Table 2 Association between RDW and all-cause and cardiovascular mortality.
Unadjusted RDW ≥ 15.5% (vs) RDW b 15.5% Model 1a RDW ≥ 15.5% (vs) RDW b 15.5% Model 2b RDW ≥ 15.5% (vs) RDW b 15.5%
All-cause mortality
CVD mortality
1.68 (1.28, 2.22), b0.001
2.15 (1.50, 3.09), b0.001
1.41 (1.04, 1.90), 0.029
1.83 (1.24, 2.70), 0.002
1.27 (0.93, 1.75), 0.132
1.60 (1.08, 2.39), 0.021
1381
Acknowledgments The authors thank Jianxiong Lin, Chunyan Yi, Xinhui Liu, Xi Xia, Richong Xu, and Chen Zhao for their assistance in data collection; all nephrologists and nurses in our PD center for their excellent management of PD patients; and Fenghua Xu and Qian Zhou for their assistance in statistical analyses. References
CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; RDW, red blood cell distribution width. a Adjusted for age, gender, diastolic blood pressure, Charlson comorbidity index, 24 h urine output divided by 100, N/L, serum albumin, triglyceride, serum urea nitrogen. b Adjusted for model 1 covariates and hemoglobin and use of erythropoietin, chalybeatus and folic acid.
Supplementary data to this article can be found online at http://dx. doi.org/10.1016/j.ijcard.2014.08.030. Funding source This work was supported by the Key Clinical Program of the Ministry of Health, China (2010-439), Guangdong Natural Science Foundation of China (9151008901000051, S2011010005077, and S2013010016002), National Basic Research Program of China (Grant No. 2011CB504000) and Guangzhou Committee of Science and Technology, China (Grant No. 2010U1-E00831). Conflict of interest The authors stated that there are no conflicts of interest.
[1] Liu X, Guo Q, Feng X, et al. Alkaline phosphatase and mortality in patients on peritoneal dialysis. Clin J Am Soc Nephrol 2014;9:771–8. [2] Molnar MZ, Mehrotra R, Duong U, Kovesdy CP, Kalantar-Zadeh K. Association of hemoglobin and survival in peritoneal dialysis patients. Clin J Am Soc Nephrol 2011;6: 1973–81. [3] Karnad A, Poskitt TR. The automated complete blood cell count. Use of the red blood cell volume distribution width and mean platelet volume in evaluating anemia and thrombocytopenia. Arch Intern Med 1985;145:1270–2. [4] Forhecz Z, Gombos T, Borgulya G, Pozsonyi Z, Prohaszka Z, Janoskuti L. Red cell distribution width in heart failure: prediction of clinical events and relationship with markers of ineffective erythropoiesis, inflammation, renal function, and nutritional state. Am Heart J 2009;158:659–66. [5] Perlstein TS, Weuve J, Pfeffer MA, Beckman JA. Red blood cell distribution width and mortality risk in a community-based prospective cohort. Arch Intern Med 2009;169: 588–94. [6] Kim CH, Park JT, Kim EJ, et al. An increase in red blood cell distribution width from baseline predicts mortality in patients with severe sepsis or septic shock. Crit Care 2013;17:R282. [7] Cavusoglu E, Chopra V, Gupta A, et al. Relation between red blood cell distribution width (RDW) and all-cause mortality at two years in an unselected population referred for coronary angiography. Int J Cardiol 2010;141:141–6. [8] Lambie M, Chess J, Donovan KL, et al. Independent effects of systemic and peritoneal inflammation on peritoneal dialysis survival. J Am Soc Nephrol 2013;24:2071–80. [9] Peev V, Nayer A, Contreras G. Dyslipidemia, malnutrition, inflammation, cardiovascular disease and mortality in chronic kidney disease. Curr Opin Lipidol 2014;25: 54–60. [10] Patel KV, Mohanty JG, Kanapuru B, Hesdorffer C, Ershler WB, Rifkind JM. Association of the red cell distribution width with red blood cell deformability. Adv Exp Med Biol 2013;765:211–6.
