Study On Correlation Between Red Blood Cell Distribution Width And Cardiovascular Events And Mortality In Hemodialysis Patients

Background:Cardiovascular Disease (CVD) is of upmost significance in prognosis in the patients of chronic kidney disease (CKD), which accounts for 44%-51% death. It was confirmed that CVD is the chief cause of death in these patients, and the incidence of cardiovascular disease is 5-10 times greater in dialysis patients than general population of the same age . In China,51% dialysis patients died of cardio-cerebrovascular disease. As the wide application of dialysis therapy in the recent years, the number of dialysis patients is increasing at an annual rate of 11%. Under the literacy education and medicare program, hemodialysis remains the chief way of renal replacement therapy. Therefore, it is important to screen practical markers which can predict cardiovascular disease in hemodialysis patients.Red blood cell distribution width is a component of the complete blood count, which can reflect the variability in the size of circulating erythrocytes. If increased, it defines a rise in the number of immature red blood cells (RBC) in peripheral blood, which may be due to the destruction of red blood cells. Combined with the mean corpuscular volume (MCV), red blood cell distribution width is often used in the differential diagnosis of anemia. Studies found that the red blood cell distribution width (RDW) had emerged as a powerful predictor of all-cause mortality and cardiovascular mortality in variety of primary cardiovascular disease, especially for ischemic heart disease (IHD) like acute myocardial infarction (AMI), coronary artery disease (CAD). Relationship had been found in red blood cell distribution width and all-cause mortality in end stage renal disease (ESRD) patients, including hemodialysis and peritoneal dialysis. However, no data are available on the association between RDW and cardiovascular mortality, cardiovascular events in maintenance hemodialysis patients.Part 1 Correlation between red blood cell distribution width and cardiovascular events in hemodialysis patientsObjectiveStudies found that the red blood cell distribution width (RDW) had emerged as a powerful predictor of all-cause mortality and cardiovascular mortality in variety of primary cardiovascular disease, especially for ischemic heart disease (IHD). However, no data are available on the association between RDW and cerebral stroke in maintenance hemodialysis(MHD)patients. The aim of this study was to evaluate the correlation between red blood cell distribution width (RDW) and cerebral stroke risk in hemodialysis patients.MethodsA total of 442 adult patients treated with hemodialysis at Guangdong General Hospital were enrolled in this study. The subjects’ demographic characteristics and laboratorial examinations were collected as baseline data, including history of cardiovascular disease, urea clearance index (Kt/v); anemia indexes:red blood cell distribution width, Fe2+concentration, ferritin level, transferrin saturation, transferrin, and the use of erythropoietin, ferric carboxymaltose or oral iron; biochemical indexes: C-reactive protein, CRP), albumin, fasting blood glucose (FBG), blood lipid and so on. RDW was described as the mean value of all measurements, and the RDW measured during the period of active hemorrhage and within 4 months after hemorrhage was excluded.Occurrences of cerebral stroke were examined until 30 June 2015. The diagnosis of cerebral stroke was confirmed by using computed tomography (CT) or magnetic resonance (MR) scan, and cerebral stroke was classified into cerebral infarction and cerebral hemorrhage.ResultsThere were no significant differences in the gender, Charlson comorbidity score, history of ischemic heart failure, albumin or blood lipid level between four groups; however, age, dialysis vintage and incidence of hypertension, hemoglobin, Fe2+and C-reactive protein were differences among the groups.RDW was found to positively correlate with C-reactive protein (CRP) level, age, and dialysis vintage, and negatively correlate with hemoglobin level, albumin level, Fe2+concentration, and transferrin saturation. RDW had nothing to do with Charlson comorbidity score, the use of EPO or ferric carboxymaltose.The subjects received a median follow-up of 50 (27,65) months.Of 442 maintenance hemodialysis patients,142 (32%) had a new-onset cardiovascular event during follow-up.58 people (12.7%) had ischemic heart failure,52 people (11.8%) had heart failure,49 people (11.1%) had symptomatic arrhythmias,40 people (9.0%) had atrial fibrillation,62 people (14.0%) had stroke, among which 41 people (9.3%) had cerebral infarction and 21 people had (4.8%) had cerebral hemorrhage.A significantly higher RDW was measured in patients with cerebral stroke [16.5 (15.5,18.0)] and cerebral infarction [16.5 (15.5,18.0)] than in non-stroke patients [16.0 (15.0,17.0)] (P= 0.003 and 0.011); however, no significant difference was seen in RDW between the cerebral hemorrhage patients and non-stroke patients.Baseline characteristics were compared according to the occurrence of cerebral stroke. There were advanced age, higher Charlson comorbidity score, and higher occurrence of hypertension, diabetes and lower transferrin saturation, albumin in the stroke group. And no difference was seen in hemoglobin, blood lipid, electrolyte between the two groups.In the univariate Cox proportional hazard model, higher red blood cell distribution width is an independent risk factor of cerebral stroke and cerebral infarction. After adjusted for age, albumin, Charlson comorbidity score, the patients with the highest quartile of RDW had a 3.55 times (hazard ratio= 3.55,95% CI: 1.33-9.51) higher risk to develop cerebral infarction in relative to those with the lowest quartile of RDW, and RDW was not an independent risk factor of cerebral hemorrhage.ConclusionQuartile of red blood cell distribution width was employed as the cutoff point for subgroup analysis. Compared with the lowest quartile of RDW, there were advanced age, longer dialysis vintage, higher incidence of hypertension, higher level of C-reactive in the highest quartile of RDW, and lower hemoglobin, transferrin saturation or concentration of Fe2+.RDW was found to positively correlate with C-reactive protein (CRP) level, age, and dialysis vintage, and negatively correlate with hemoglobin level, albumin level, Fe2+concentration, and transferrin saturation.Compared with the non-stroke group, there were advanced age, higher Charlson comorbidity score, and higher occurrence of hypertension, diabetes and lower transferrin saturation, albumin in the stroke group.In comparison with non-stroke group, the RDW level was higher in the stroke and cerebral infarction group. In the other hand, the incidence of cerebral stroke and cerebral infarction were much higher in the higher quartiles of RDW than the lower ones.The increased RDW was an independent risk factor of cerebral infarction in patients undergoing hemodialysis.Part 2 Correlation between red blood cell distribution width and mortality in hemodialysis patientsObjective:Red blood cell distribution width had been proved to be associated with poor prognosis in cardiovascular disease patients, particularly in acute myocardial infarction, coronary artery disease, angina. Association was reported between red blood cell distribution width and cardiovascular mortality, all-cause mortality in peritoneal dialysis patients. And this study was conducted to assess the correlation between RDW and all-cause mortality, cardiovascular mortality in hemodialysis patients.Methods:A total of 442 adult patients treated with hemodialysis at Guangdong General Hospital were enrolled in this study. The subjects’ demographic characteristics and laboratorial examinations were collected as baseline data, including history of cardiovascular disease, urea clearance index (Kt/v); anemia indexes:red blood cell distribution width, Fe2+ concentration, ferritin level, transferrin saturation, transferrin, and the use of erythropoietin, ferric carboxymaltose or oral iron; biochemical indexes: C-reactive protein, CRP), albumin (ALB), fasting blood glucose (FBG), blood lipid and so on. RDW was described as the mean value of all measurements, and the RDW measured during the period of active hemorrhage and within 4 months after hemorrhage was excluded.In this study, quartile of red blood cell distribution width was employed as the cutoff point for subgroup analysis. Screen parameters that may relate to red blood cell distribution width by comparing clinical characteristic between the four groups, and correlation analysis is applied.Deaths from all-causes, cardiovascular were examined until 30 June 2015. The risk factors of mortality was identified with a multivariate Cox proportional hazard model.Results:Quartile of red blood cell distribution width was employed as the cutoff point for subgroup analysis. With a median follow-up of 50 (27,65) months, of the 442 MHD patients,177 (40%) died as a result of all-causes,95 (21.5%) died from CVD. A significantly higher RDW was observed in death group than in survival group [16.3 (15.4,17.0) vs.16.0 (15.0,16.8), P<0.001]. Further more, the patients died from cardiovascular disease were found to have a significantly higher RDW than survival group [16.5 (15.8,17.4) vs.16.0 (15.0,16.8), P<0.001].In the univariate Cox regression analysis, higher red blood cell distribution width is a risk factor of all-cause mortality and cardiovascular mortality. In the Cox proportional hazard model after adjustment for multi-factors, RDW remained an independent risk factor of cardiovascular mortality, rather than all-cause mortality. Compared with the lowest quartile of RDW, the adjusted HR for cardiovascular mortality of the highest quartile was 2.15 [95% confidence interval (CI) 1.15-4.04].Conclusion:In comparison with survival group, the RDW level was higher in the patients died from cardiovascular disease and all-cause. On the other hand, the incidence of cardiovascular mortality and all-cause mortality were much higher in the higher quartiles of RDW than the lower ones.Red blood cell distribution width is the independent risk factor of cardiovascular mortality, rather than all-cause mortality.