Year : 2007 | Volume
: 18 | Issue : 1 | Page : 31--36
Association of White Blood Cell Count with Left Ventricular Hypertrophy and Ejection Fraction in Stable Hemodialysis Patients
Department of Internal Medicine, Hajar Medical, Educational and Therapeutic Center, Shahrekord University of Medical Sciences, Shahrekord, Iran
Department of Internal Medicine, Shahrekord University of Medical Sciences, Shahrekord
Cardiovascular disease is the principal cause of morbidity and mortality in dialysis patients, and left ventricular hypertrophy (LVH) is an independent risk factor for mortality in hemodialysis (HD) patients. This analysis was undertaken to explore the associations of white blood cell (WBC) count with LVH and also left ventricular (LV) ejection fraction in patients on regular HD. There were 36 patients in the study, of whom 21 were males and 15 females. Their mean (± SD) age was 46 ± 17 years. The median length of the time the patients had been on HD was 19 months. The mean (± SD) WBC count of the patients was 5660 ± 2000 cells/mm 3 (median: 5500 cells/mm 3 ). The mean (± SD) LV ejection fraction of the study patients was 48 ± 11.5 % (median: 52 %). On the basis of septal thickness, the patients were stratified into groups with no, mild, moderate, and severe LVH. In this study, a significant inverse association between WBC count and LV ejection fraction and a significant positive correlation between WBC count and stages of LVH were seen. Our study shows a significant effect of WBC count on LV function and structure. Additional studies are needed to determine whether interventions to decrease inflammation during HD can reduce the risk for LVH associated with elevated WBC count.
|How to cite this article:|
Nasri H. Association of White Blood Cell Count with Left Ventricular Hypertrophy and Ejection Fraction in Stable Hemodialysis Patients.Saudi J Kidney Dis Transpl 2007;18:31-36
|How to cite this URL:|
Nasri H. Association of White Blood Cell Count with Left Ventricular Hypertrophy and Ejection Fraction in Stable Hemodialysis Patients. Saudi J Kidney Dis Transpl [serial online] 2007 [cited 2020 Jul 15 ];18:31-36
Available from: http://www.sjkdt.org/text.asp?2007/18/1/31/31842
Cardiovascular disease is the most common cause of death in patients with end-stage renal disease (ESRD) and accounts for much of the morbidity in this population.  Dialysis patients are prone to developing atherosclerosis and consequent ischemic heart disease. Additionally, primary myocardial dysfunction and overt heart failure also are highly prevalent. At the initiation of therapy for ESRD, eightyfour percent of patients have left ventricular hypertrophy (LVH), left ventricular (LV) dilatation, or low fractional shortening. Also, LVH has been found in 38% of patients with chronic renal failure (CRF) prior to the requirement of dialysis. , The presence of LVH or LV dilatation (or both) is clearly a poor prognostic factor. ,, Left ventricular hypertrophy is the consequence of combined effects of chronic hemodynamic overload and non-hemodynamic biochemical and neurohumoral factors characteristic of uremia. LVH is an independent risk factor for mortality in hemodialysis (HD) patients. , Indeed, many conventional cardiovascular risk factors in the general population are not as predictive in patients with ESRD.
The absolute neutrophil count and total white blood cell (WBC) count are associated with adverse cardiovascular outcomes and mortality,  since they serve as important biomarkers for these disease processes. Elevated WBC count is also considered a risk factor for acute myocardial infarction, coronary artery disease, and stroke.  The WBC count decreases during HD and is considered to be related to the use of different dialysis membranes.  It was shown that hollow-fiber dialyzers activate complement by releasing C3a, C3d, and C5a levels which peak 15 minutes after beginning dialysis. Total WBC counts dropped simultaneously by 76%, and the decrease in leukocytes was inversely correlated with the levels of C3a, C3d, and C5a.  Indeed, there is increased inflammatory activity in the majority of patients undergoing HD. Activation of the immune system during treatment with various dialyzer membranes is one of the causes of this inflammatory status. The result of these activations is the release of inflammatory mediators. , Studies concerning the association of WBC count and left ventricular function and structure in HD patients are quiet scarce. We therefore undertook this analysis to explore the association of WBC count with LVH and LV ejection fraction in ESRD patients on regular HD.
Patients and Methods
This cross-sectional study was carried out on patients with ESRD undergoing maintenance HD. According to the severity of anemia, patients were given intravenous (i.v.) iron sucrose in varying doses after each dialysis session. All patients were also given folic acid, 3 mg daily, L-carnitine, 750 mg daily, B-complex tablets, and 2000 units of i.v. Eprex [recombinant human erythropoietin (rHuEPO)] after each dialysis session routinely. Exclusion criteria were presence of active or chronic infection, usage of drugs that affect bone marrow activity, history of cigarette smoking, and the presence of pericardial effusion on echocardiography.
Blood samples were collected after overnight fasting for complete blood count (CBC), including total and differential WBC count, which were measured using a SysmexKX-21N Cell counter within 30 minutes from taking the blood samples. Also, levels of serum C-reactive protein (CRP), calcium (Ca), phosphorus (P), iron, albumin (Alb), and ferritin [radioimmunoassay (RIA)] were measured using standard methods. Intact serum parathormone (iPTH) was measured by the RIA method using DSL-8000 kits from the USA (normal range of values is 10-65 pg/ml). Echocardiography was performed in all patients by a single cardiologist who was unaware of the patients' data and history.
On the basis of septal thickness, left ventricular hypertrophy was stratified into no (septal thickness between 6 and 11 mm), mild (septal thickness between 11 and 15 mm), moderate (septal thickness between 15 and 18 mm), and severe (septal thickness >18 mm) LVH. , LVH measurements were done at the end-diastolic phase. An LV ejection fraction between 55 and 75% was considered normal. , All of the study patients were hypertensive, which was controlled with amlodipine and/or atenolol in varying doses.
For statistical analysis, descriptive data are expressed as mean ± SD, median values, and frequency distributions. For correlations, partial correlation and Kruskal Wallis tests were used. All statistical analyses were performed using the SPSS (version 11.5.00). Statistical significance was set at p value 3 (median: 5500 cells/mm 3 ). The mean ± SD of the LV ejection fraction of all patients was 48 ± 11.5 percent (median = 52 %). A significant positive correlation was found between WBC count and stages of LVH (p = 0.025).
A significant inverse correlation was seen between the WBC count with LV ejection fraction [Figure 1] (r = 0.37, p = 0.045) (adjusted for age, duration, and dose of dialysis, as well as serum iPTH, phosphorus, and ferritin).
In this study, we found an inverse association between WBC count and LV ejection fraction and a significant positive correlation of WBC count with stages of LVH. An association between elevated WBC count and mortality due to coronary heart disease (CHD) has been previously observed.  Brown et al  studied 8914 adults aged 30-75 years to examine the association between WBC count and CHD [the NHANES II Mortality Study (1976-1992)]. Mortality, with Cox regression analyses of data, was greater among persons who had high WBC counts, and the most common cause of death was CHD. Compared to persons with WBC counts 7.6 were at an increased risk of death from CHD after adjustment for smoking status and other risk factors. Similar results were observed among non-smokers as well. They concluded that higher WBC counts are a predictor of CHD mortality independent of the effects of smoking and other traditional CVD risk factors, which may indicate a role for inflammation in the pathogenesis of CHD.  Horne et al.  conducted a study to determine the predictive ability of total WBC count and its subtypes for risk of death or developing myocardial infarction (MI) on a total of 3,227 patients with a mean age of 63 years. They found that 65% had CAD. In multivariable modeling, entering standard risk factors, presentation, and CAD severity, the total WBC count was an independent predictor of death/MI. They concluded that, firstly, the total WBC count is confirmed to be an independent predictor of death/MI in patients with, or at high risk for development of, CAD, and secondly, a greater predictive ability is provided by high neutrophil count. The greatest risk prediction is given by the neutrophil/lymphocyte ratio.  In another study, Lee et al. examined the association between WBC count and incidence of coronary heart disease, ischemic stroke, and mortality from cardiovascular disease in 13,555 African-American and white men and women [The Atherosclerosis Risk in Communities (ARIC) Study]. They showed that elevated WBC count is directly associated with an increased incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in these groups.  .Interestingly, Uesugi et al  attempted to test the hypothesis that the circulating WBC and neutrophil counts are related to LV indices in patients with the same risk area for MI. They examined 100 consecutive patients with MI who had a lesion at segment-6 according to the American Heart Association classification and who underwent successful direct coronary angioplasty. Their study revealed that the circulating WBC count correlated with function and volume of the successfully reperfused LV after MI, indicating that the WBC count needs to be taken into consideration as an independent factor affecting the LV indices.
These results suggest that higher WBC counts are a predictor of mortality due to CHD independent of the effects of smoking and other traditional CVD risk factors, which may indicate a role for inflammation in the pathogenesis of CHD. We also found a positive correlation between WBC count and LVH and an inverse association with left ventricular ejection fraction in a group of stable HD patients. To our knowledge, this is the first study addressing the significance of WBC count in LV function and structure. Additional studies are needed to determine whether interventions to decrease inflammation during HD can reduce the risk for LVH associated with elevated WBC count.
We would like to thank Dr. F. Roghani, a cardiologist from our hospital for performing the echocardiograms.
|1||Rahn KH, Barenbrock M, Hausberg M, et al. Vessel wall alterations in patients with renal failure.Hypertens Res 2000;23(1):3-6.|
|2||Murphy SW, Foley RN. Cardiac disease in dialysis patients, divalent ion abnormalities and hyperparathyroidism in the etiology of cardiovascular disease of patients with chronic renal failure. Semin in Dial 1999;12(2):97-101.|
|3||Zoccali C, Benedetto FA, Mallamaci F, et al. Prognostic impact of the indexation of left ventricular mass in patients undergoing dialysis J A Soc Nephrol 2001;12: 2768-74.|
|4||Nasri H, Baradaran A, Naderi A.S. Close association between parathyroid hormone and left ventricular function and structure in end-stage renal failure patients under maintenance hemodialysis. Acta Med Austriaca 2004;31(3):67-72.|
|5||Meeus F, Kourilsky O, Guerin AP, Gaudry C, Marchais SJ, London GM. Pathophysiology of cardiovascular disease in hemodialysis patients. Kidney Int Suppl 2000;76:S140-7.|
|6||Murphy ST, Parfrey PS.The impact of anemia correction on cardiovascular disease in end-stage renal disease. Semin Nephrol 2000;20(4):350-5.|
|7||Nasri H, Baradaran H. Effect of anemia on left ventricular hypertrophy and ejection fraction in maintenance hemodialysis patients. Timok Med J 2005;30(2): 63-67.|
|8||Reddan DN, Klassen PS, SZczech LA, et al. White blood cells as a novel mortality predictor in haemodialysis patients. Nephrol Dial Transplant 2003;18(6):1167-73.|
|9||Brown DW, Giles WH, Croft JB. White blood cell count: an independent predictor of coronary heart disease mortality among a national cohort. J Clin Epidemiol 2001;54:316-22.|
|10||Ksiazek A, Sokolowska G, Marczewski K, Solski J.Leukopenia with different regenerated haemodialysis membranes. Int Urol Nephrol 1984;16(1):61-7.|
|11||Wegmuller E, Montandon A, Nydegger U, Descoeudres C.Biocompatibility of different hemodialysis membranes: activation of complement and leukopenia. Int J Artif Organs 1986;9(2):85-92.|
|12||Brown DW, Giles WH, Croft JB,White blood cell count: an independent predictor of coronary heart disease mortality among a national cohort. J Clin Epidemiol 2001;54(3):316-22.|
|13||Horne BD,Anderson JL, John JM, et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol 2005 17;45(10):1638-43.|
|14||Lee CD, Folsom AR, Nieto FJ, et al. White blood cell count and incidence of coronary heart disease and ischemic stroke and mortality from cardiovascular disease in AfricanAmerican and White men and women: atherosclerosis risk in communities study. Am J Epidemiol 2001; 154(8):758-64.|
|15||Uesugi T, Iwasaki K, Murakami M, et al. Circulating white blood cell count correlates with left ventricular indices independently of the extent of risk area for myocardial infarction after successful reperfusion. Acta Cardiol 2004;59(5):533-9.|