1 Second Department of Internal Medicine, Nihon University School of Medicine, 2 Department of Hemodialysis, Toshima Chuo Hospital and 3 Nihon University Graduate School of Business, Tokyo, Japan
Correspondence and offprint requests to: Dr Tatsuyuki Yamauchi, Second Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173, Japan. Email: yama8880{at}yahoo.co.jp
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Abstract |
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Methods. We classified 77 non-diabetic haemodialysis patients into low VF, middle VF and high VF groups after determining VF area using computed tomography. Systemic atherosclerosis was assessed from intima-media thickness (IMT), plaque score (PS) and stiffness parameter ß (stiffness-ß) measured by high-resolution B-mode ultrasonography.
Results. Compared with the low VF group, the high VF group exhibited (i) significantly higher fasting plasma insulin (11.0 ± 6.8 vs 7.1 ± 2.9 µU/ml, P = 0.0061); (ii) significantly higher plasma triglycerides (141.8 ± 94.0 vs 86.5 ± 32.5 mg/dl, P = 0.0032); and (iii) significantly lower plasma high-density lipoprotein cholesterol (42.1 ± 14.5 vs 53.0 ± 15.7mg/dl, P = 0.0134). Moreover, the high VF group had a higher prevalence and extent of carotid atherosclerosis: IMT was 0.69 ± 0.13 vs 0.61 ± 0.12 mm (P = 0.0239), PS was 4.8 ± 3.2 vs 2.4 ± 3.6 (P = 0.0236) and stiffness-ß was 11.4 ± 3.1 vs 8.5 ± 3.0 (P = 0.0082) in the high and low VF groups, respectively.
Conclusion. We show that VF is associated with the prevalence of carotid atherosclerosis as well as with hyperinsulinaemia and lipid abnormalities in chronic haemodialysis patients.
Keywords: carotid atherosclerosis; haemodialysis; intima-media thickness; multiple risk factors; ultrasonography; visceral fat
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Introduction |
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In recent decades, the development of renal replacement therapy has improved both the physical condition and survival rate of haemodialysis patients. Therefore, obesity may present a risk factor for atherosclerosis, especially in contemporary healthy haemodialysis patients. In support of this, recent studies have demonstrated a strong association between visceral fat (VF) accumulation and systemic atherosclerosis in the general population [5]. Furthermore, Odamaki et al. [6], while investigating abdominal fat distribution in haemodialysis patients, found that they had an excessive VF accumulation relative to healthy subjects. Thus, VF in haemodialysis patients may accelerate systemic atherosclerosis, as it does in the general population.
The purpose of the present study was to investigate associations between VF as well as multiple risk factors and the prevalence of carotid atherosclerosis in stable haemodialysis patients. We evaluated VF accumulation in haemodialysis patients by the computed tomography (CT) scanning technique and determined the prevalence and extent of carotid atherosclerosis using high-resolution B-mode ultrasonography.
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Subjects and methods |
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The patients were maintained on regular haemodialysis three times a week for 44.5 h/day using hollow-fibre dialysers with a bicarbonate-buffered dialysate. The blood flow rate ranged from 180 to 260 ml/min, with a dialysate flow rate of 500ml/min. Body weight was measured before and after each dialysis, and the post-dialysis body weight served as the dry weight.
Measurement of body fat mass and VF
Body-mass index (BMI) was calculated as the post-dialysis dry weight in kilograms divided by the square of the height in metres. The percentage fat was measured by bioelectrical impedance analysis. The body fat distribution was determined using the CT scanning technique, according to the procedure of Tokunaga et al. [7]. All CT scans were performed with the subject in the supine position using a slip ring CT scanner (Radix-Pratico, Hitachi, Tokyo, Japan). The subcutaneous fat layer was clearly defined as the extraperitoneal fat between skin and muscle, with attenuation ranging from -40 to -140 HU. The intraperitoneal portion, having the same density as the subcutaneous fat layer, was defined as the visceral fat area (VFA). The subcutaneous fat area (SFA) and intra-abdominal VFA were measured at the level of the umbilicus.
Evaluation of carotid atherosclerosis by B-mode ultrasonography
Ultrasonography of the carotid arteries was performed with an echotomography system (Logic 400, GE Yokogawa Medical Systems, Tokyo, Japan) and an electrical linear transducer (midfrequency of 11 MHz).
Carotid intima-media thickness. Carotid intima-media thickness (IMT), as defined by Salonen et al. [8,9], was measured as the distance from the leading edge of the first echogenic line to that of the second echogenic line. The first line represented the lumenintima interface, and the second line represented the collagen-containing upper layer of the adventitia. Three IMT measurements were made in the far wall of both the right and left common carotid arteries (CCAs) at the site of the greatest IMT for each recording and vessel. The mean of these six IMT measurements was used to derive an estimate of the overall IMT in the CCAs. Atherosclerotic lesions were defined as plaques when IMT was 1.0 mm in the CCAs below the carotid bulb.
The plaque score. The plaque score (PS), as defined by Handa et al. [10], was computed by summing the maximum thickness of the intima-media complex (plaque thickness), measured in millimetres, on the near and far walls of each of four divisions on both sides of the carotid arteries: S1 was the region of the internal carotid artery (ICA) <15 mm distal to its bifurcation from CCAs; S2 was the region of ICA and CCAs <15 mm proximal to the bifurcation; S3 was the region of CCAs >15 mm and <30 mm proximal to the bifurcation; and S4 was the region of CCAs >30 mm proximal to the bifurcation below the flow divider. The length of the individual plaques was not considered in determining the PS.
The stiffness parameter ß. The stiffness parameter ß (stiffness-ß) is a quantitative index of the elastic properties of large arteries. We measured the vascular internal diameter of the carotid artery and calculated stiffness-ß according to the method of Kawasaki et al. [11] using the following equation:
ß = [logePs/Pd] x Dd/(Ds-Dd)
where Ps is systolic pressure, Pd is diastolic pressure, Ds is the inner diameter at systole and Dd is the inner diameter at diastole. ß is a coefficient when the constitutive stressstrain relation is expressed as an exponential function, representing the stiffness of the vascular wall.
Analytical procedures
Blood samples were drawn for biochemical analysis after an overnight fast. Plasma triglycerides, total cholesterol and high-density lipoprotein cholesterol (HDL-C) concentrations were determined using standard enzymatic techniques with an automatic analyser. Plasma glucose concentrations were measured using the glucose oxidase method. Plasma insulin was assayed using a double antibody radioimmunoassay.
Statistical analysis
Given the small number of reports examining VF in haemodialysis patients, we separated our patients into three equal groups, designated low VF, middle VF and high VF, based on the ranking of VFA of males and females, respectively. Results are shown as means ± SD. Differences between groups were analysed by one-way ANOVA followed by Fishers PLSD tests. Spearmans rank correlations evaluated relationships between BMI, SFA or VFA and variables obtained by blood samplings and B-mode ultrasonography. Multiple regression models of BMI, SFA or VFA were performed with various parameters. P-values of <0.05 were considered to be statistically significant.
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Results |
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Discussion |
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Nakamura et al. [5] described the visceral fat syndrome in the general population as a highly atherogenic state associated with multiple risk factors that stems from VF accumulation. Our findings indicate that this syndrome is also present in the dialysis population.
Prior to our study, only Odamaki et al. [6] had evaluated VF parameters in the dialysis population using CT scanning techniques that were similar to the techniques used by our group. As in our study, they demonstrated that VF accumulation correlated well with serum lipid abnormalities. In addition, we found that VF accumulation had a good correlation with abnormalities in carbohydrates.
The main objective of the present study was to examine whether systemic atherosclerosis is associated with VF accumulation in haemodialysis patients, as it is in the general population. We found a good correlation between VF accumulation and carotid atherosclerosis, which may be representative of systemic atherosclerosis. VF may contribute to the accelerated atherosclerosis in haemodialysis patients and may thus represent an additional risk for atherosclerotic disease in this patient population.
Recently, Leavey et al. [17] reported that increasing body size (BMI) was correlated with a decreased mortality risk even in healthier haemodialysis patients. This correlation does not contradict our result, since BMI itself was not correlated with any indices of carotid atherosclerosis in our population. Moreover, our study suggests the possibility of an increased mortality risk from systemic atherosclerosis, particularly among haemodialysis patients that are relatively obese but have VF accumulation.
Compared with the general population, haemodialysis patients are already characterized by abnormalities in lipid and carbohydrate metabolism. For example, repeated use of heparin during haemodialysis produces alterations in lecithin cholesterol acyltransferase activity that may contribute to lipid abnormalities specific to haemodialysis conditions [18]. Similarly, accumulation of uraemic toxins, metabolic acidosis and reductions in insulin clearance are thought to contribute to insulin resistance in haemodialysis patients [19,20]. Even though haemodialysis therapy has been improved recently, it remains difficult to eliminate these disadvantages. On the other hand, it may be easier to modify patient lifestyle to prevent the accumulation of VF along with its associated risk factors to thereby slow the development of atherosclerosis, especially in contemporary healthy haemodialysis patients. It is therefore important for these patients to avoid high-fat diets and to exercise according to their physical abilities.
In summary, we have shown that VF accumulation in haemodialysis patients is correlated with several metabolic risk factors and the prevalence of carotid atherosclerosis. Thus, VF accumulation may contribute to atherosclerosis in haemodialysis patients, especially if they are relatively healthy patients. However, because the present study represented a cross-sectional investigation in a smaller population, further longitudinal investigations in larger populations will be required to clarify the contribution of VF to systemic atherosclerosis in haemodialysis patients.
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Acknowledgments |
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Conflict of interest statement. None declared.
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References |
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