Effect of anemia on left ventricular hypertrophy and ejection fraction in maintenance hemodialysis patients

Hamid Nasri(1), Azar Baradaran(2)
(1) Shahrekord University of Medical Sciences, Hajar Medical, Educational and Therapeutic Center, Nephrology Research Center (Section of Hemodialysis)
(2) Department of Biochemistry, The Center of Research and Reference Laboratory of Iran Hospital Bu Ali, Damavand St. Tehran

Note: summary in Serbian
Napomena: sažetak na srpskom jeziku

INTRODUCTION

Cardiovascular disease is the principal cause of morbidity and mortality in dialysis patients [1-2]. The principal alterations responsible are left ventricular hypertrophy and arterial disease [2]. Left ventricular hypertrophy (LVH) is the consequence of combined effects of chronic hemodynamic overload and nonhemodynamic biochemical and neurohumoral factors characteristic of uremia. LVH is an independent risk factor [2-4]. In recent years much progress has been made in understanding the pathogenesis of cardiovascular disease in the uraemic population [4]. Anaemia is a consistent finding in chronic renal disease, affecting up to 90% of patients, and the central role of anaemia in the development of cardiovascular dysfunction is now well established [5-6], Pathophysiologically chronic anemia, long-lasting flow/volume overload and increased cardiac work lead to progressive cardiac enlargement and left ventricular hypertrophy [7]. The risk of coronary heart disease (CHD) increases when the anemia is not treated, and recent studies have indicated that anemia in patients with chronic renal failure may predispose to ischemic heart disease, heart failure, and premature death [7-9]. Therefore, the risk of CHD may be distinctly higher in people with renal insufficiency and concomitant anemia, when compared with people with renal insufficiency but without anemia and with people with normal renal function [7-10]. A significant proportion of patients have established cardiovascular complications on initiation of dialysis, raising the possibility of early correction of anaemia as a strategy for preventing cardiovascular co-morbidities among renal patients [10-12]. It is thought that anaemia can increase the severity of heart failure and is associated with a rise in mortality, hospitalization and malnutrition. Anaemia can also further worsen renal function and cause a more rapid progression to dialysis than is found in patients without anaemia [10-13]. Partial correction of anemia with recombinant human erythropoietin likely reduces left ventricular mass and volume. Complete correction of anemia may prevent progressive left ventricular dilatation in patients with normal left ventricular volumes[3]. In the present work we aimed to consider the adverse effects of amenia on left venrticular function and structure in our hemodialysis patients.

PATIENTS AND METHODS

This study is cross-sectional that was conducted on patients with end-stage renal disease (ESRD), undergoing maintenance hemodialysis treatment. According to the severity of anemia, patients were under IV iron thereapy with Hemopher with various doses after each dialysis session. All patients were under 3mg folic acid daily, 750mg L-carnitine daily, one IV B-complex ampule after each dialysis session, and 2000U IV Eprex (recombinant human erythropoietin(rHuEPO) afer each dialysis session routinely. For patients, complete blood count, serum Iron, total iron binding capacity and serum ferritin by RIA method were measured, mentioned laboratory test were measured by standard kits. On the basis of septal thickness, we stratified the patients into no LVH (septal thickness between 6-11 mm), mild (septal thickness between 11-15 mm), moderate(septal thickness between 15-18 mm) and severe LVH (septal thickness >18 mm). LVH measurements were done at the end diastolic phase. Percent of cardiac ejection fraction between 55 to 75% was considered normal. The presence of cardiac chest pain was considered positive with its' typical presentation , past history of ischemic heart disease as well as its' drammatic response to nitroglycerine treatment [4]. Duration and doses of hemodialysis treatment were calculated from patient's records and the duration of each hemodialysis session was four houre. For statistical analysis descriptive data are expressed as Mean± SD. Comparison between groups were considered using T test. For correlations we used X², Pearson, Spearman's rho, Kruskal-Walis and partial correlation tests. All statistical analysis were performed using the SPSS (version 11.5.00). Statistical significance was significant when p value< 0,05.

RESULTS

The total patients were 60 (F=21 M=39), consisting of 44 non diabetic hemodialysis patients (F=15 M=29), and 16 diabetic hemodialysis patients (F=6 M=10). Table 1 shows the Mean±SD of age, the length of the time that patients had been on hemodialysis treatment, dialysis dose and the results of laboratory tests. Mean±SD of age of total patients were 46 ±18 years. The length of the time patients had been on hemodialysis were 46 ±18 months. Mean±SD of hemoglobin and hematocrit of total patients were 8,9±2 g/dl and 28±6 percent respectively. Mean±SD of LV ejection fraction of total patients were 47.9±10.4 percent, Mean±SD of diabetic and non diabetic group were 46±10 and 4846±11 percent respectively. Stage of LVH in total patients were: Stage one: 30%, stage two: 48,3%, stage three: 21,7 %, in diabetic group stage of LVH were: Stage one: 18,8 %, stage two: 56,3 %, stage three: 25% in nondiabetic patients stage of LVH were: Stage one: 34,1%, stage two: 45,5 %, stage three: 20,5 %, moreover 35% of total patients had cardiac chest pain, diabetics 56,3% and nondiabetics 27,3% had cardiac chest pain respectively. In this study significant difference of Hgb (9±2 vs 8±2 g/dl)(p= 0,053) and Hct ( 29± 6 vs 26± 5,5) (p= 0,046) between males and females of total patients were seen. No significant difference of age, serum Iron, TIBC and duration of hemodialysis treatment and also dialysis dose between males and females of total patients were seen (p>0,05). No significant difference of ferritin, serum iron, TIBC, LV ejection fraction, Hgb and Hct between diabetic and nondiabetic HD patients were seen (p>0,05). Significant inverse correlation of serum ferritin of the patients with hemoglobin level was found (r= - 0,32 p= 0,016). A near significant inverse correlation of LV ejection fraction with serum ferritin was demonstrated too (r = - 0,22 p =0,095). Significant inverse correlation of LV ejection fraction with duration of hemodialysis treatment was demonstrated too (r = - 0,25 p =0,050). Statistical analysis on left ventricular hypertrophy and its correlation showed no significant correlation of LVH with gender, hypertension, diabetes mellitus and cardiac chest pain were found (p>0,05). No significant correlation of LVH with Hgb, Hct, serum iron, TIBC, ferritin were demonstrated (p>0,05). No significant correlation of LV ejection fraction with Hgb, Hct, serum iron and TIBC were demonstrated (p>0,05) too. A significant inverse correlation of LVH with LV ejection fraction ( r = - 0,60 p <0,001) were found.

DISCUSSION

Present study showed significant difference of Hgb, Hct between males and females with more values in males. No significant difference of ferritin, serum iron, TIBC, LV ejection fraction, Hgb and Hct between diabetic and nondiabetic HD patients were seen, a significant inverse correlation of serum ferritin of the patients with hemoglobin level was found. Significant inverse correlation of LV ejection fraction with duration of hemodialysis treatment was demonstrated too and no significant correlation of LVH with gender, hypertension, diabetes mellitus and cardiac chest pain were found, no significant correlation of LVH with Hgb, Hct, serum iron, TIBC, ferritin were demonstrated , no significant correlation of LV ejection fraction with Hgb, Hct, serum iron and TIBC and a near significant inverse correlation of LV ejection fraction with serum ferritin was demonstrated also a significant inverse correlation of LVH with LV ejection fraction were found too. Jurkovitz et al. on a total of 13,329 participants conducted a study to evaluate the correlation of serum creatinin and anemia. The results were: interaction between Hgb concentration and serum creatinine (Scr) was significant among people with anemia, and a Scr 1,2 mg/dl in women or 1,5 mg/dl in men was associated with a higher risk of coronary heart disease (CHD) than those with normal Scr. In contrast, among those without anemia, this association was not noted. Jurkovitz concluded that high Scr is associated with almost a threefold risk of CHD among middle-aged people with anemia, whereas no increased risk is found in people with high Scr in the absence of anemia [14]. Rasic et al. in a one year followed up of 50 patients with end-stage renal disease by performing a serial echocardiography and serial measurements of potential modifiable cardiovascular risk factors, showed that LVH is present in high percentage (72%) in uraemic patients, even at the beginning of hemodialysis treatment and this morphological abnormality is statistically significantly related to present anaemia near patients, other factors include hypertention and hyperparathyroidism [15]. A recent analysis of the ARIC data found a 40% increased risk of CVD in subjects with anemia compared with patients with normal Hgb [8]. Low Hgb increases also the risk of death in patients with heart failure independent of renal function [9,15]. Other investigators have described a U-shaped relationship between hematocrit levels and risk of CVD [17-19]. The association between increased risk of CHD and high Scr in patients with anemia might be explained by an impairment in the physiologic mechanisms of adaptation to maintain the oxygen supply to the tissues in the presence of anemia. These mechanisms of adaptation are both nonhemodynamic and hemodynamic [7]. Nonhemodynamic mechanisms include increased erythropoietin production to stimulate erythropoiesis and increased oxygen extraction. In normal resting conditions, the nonhemodynamic factors can almost entirely compensate for Hgb deficit [7]. However in the setting of kidney disease, erythropoietin production is impaired and therefore the only nonhemodynamic mechanism of compensation is an increase in oxygen extraction, which has a limited effect [20]. When the Hgb concentration is <10 g/dl, nonhemodynamic factors become inadequate and increased cardiac output and blood flow begin to compensate for tissue hypoxia. There are three major components in the hemodynamic compensation [7]: increase in cardiac output, increase in preload as a result of higher venous return, and decrease in systemic vascular resistance as a result of arterial dilation, formation of collaterals, arteriovenous shunts, de novo angiogenesis, and decrease in blood viscosity [7,21]. Anemia has also been identified as a risk factor for left ventricular growth in patients with mild to moderate renal insufficiency [6-22]. Left ventricular hypertrophy predisposes to heart failure or ischemic heart disease and ultimately premature death [6,9,22]. In our study female hemodialysis had more prominent anemia than females which implies more attention to anemia treatment in female hemodialysis patients. We could show an associetion between LV ejection fraction and serum ferritin , we also showed that duration of hemodialysis treatment have an adverse effect on progression of left ventriculat hypertrophy thus we concluded that anemia might aggravate the LVH in conjuction with other important factors as mentioned one of them is duration of hemodialysis treatment.
Aknowlegments: Many thanks to Dr F. Roghani cardiologist of our hospital for performing all echocardiographies.

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