| Abstract|| |
Accelerated atherosclerosis is very common in hemodialysis (HD) patients and is related to morbidity and mortality. The aortic knob width (AKW), which can easily be calculated on chest radiographs has also been found to be related to atherosclerosis in patients with normal renal function. The importance of AKW in HD patients is not known. The current study is aimed to investigate factors associated with increased AKW in HD patients. The study participants had their medical history taken and a physical examination conducted, with calculation of dialysis adequacy and AKW. AKW was calculated from the chest x-rays at the end of the dialysis session, when the patients were in their dry weight. A total of 91 HD patients and 65 patients with normal renal function (as a control group) were included. The mean of the AKW was 35.0 ± 5.8 mm in HD patients and 26.6 ± 4.3 mm in the control group (P <0.0001). Stepwise linear regression analysis of both groups combined revealed that age (P: 0.001), male gender (P <0.0001), systolic BP (P <0.0001), presence of HD treatment (P: 0.016), and albumin levels (P: 0.021) were independently related with increased AKW. On the other hand, in HD patients stepwise linear regression showed that age (P <0.0001), pre-dialysis systolic BP (P: 0.003), male gender (P <0.0001), being a non-smoker (P: 0.002), total cholesterol (P: 0.001), and intact parathormone levels (P: 0.005) were independently associated with increased AKW. In conclusion, AKW is increased in HD patients when compared with the normal population. These preliminary findings may enhance the use of chest radiography as a screening method, and if confirmed, can assist risk stratification in HD patients.
|How to cite this article:|
Afsar B, Saglam M, Yuceturk C, Agca E. The relationship between aortic knob width and various demographic, clinical, and laboratory parameters in stable hemodialysis patients. Saudi J Kidney Dis Transpl 2014;25:1178-85
|How to cite this URL:|
Afsar B, Saglam M, Yuceturk C, Agca E. The relationship between aortic knob width and various demographic, clinical, and laboratory parameters in stable hemodialysis patients. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2020 May 29];25:1178-85. Available from: http://www.sjkdt.org/text.asp?2014/25/6/1178/144250
| Introduction|| |
It is well known that cardiovascular diseases are the leading cause of death in hemodialysis (HD) patients and accelerated atherosclerosis is the major contributing factor in these patients.  Both traditional (e.g., advanced age, smoking, diabetes mellitus, hypertension, and dyslipidemia) and non-traditional risk factors (e.g., inflammation, malnutrition, oxidative stress, vascular calcification) play a role in the development of accelerated atherosclerosis in these patients.  Thus, it is important to detect atherosclerotic lesions and factors related to this condition. However, arterial disease does not begin with the first clinical event, but develops much earlier, without overt symptoms.  Therefore, identifying asymptomatic individuals with subclinical atherosclerosis may be considered the best screening test for predicting subsequent events, such as chronic heart disease, and offering them aggressive risk-reduction therapy. Hence, in recent years, great emphasis has been placed on identifying patients with subclinical atherosclerosis. ,, Although many sophisticated and expensive diagnostic procedures are available to detect atherosclerosis [e.g., conventional or computerized tomography (CT) angiography] these tests are not suitable for large patient populations or for asymptomatic patients and there is a need for simple and inexpensive tests to assist in the evaluation of atherosclerosis in HD patients. In recent times, the aortic knob width (AKW), which can easily be calculated by simple chest radiographs, has been shown to be associated with subclinical atherosclerosis in patients with normal renal function.  It has also been shown that increased AKW has been associated with various cardiovascular risk factors, such as, hypertension, diabetes, increased vascular stiffness, and calcification. , Both traditional and non-traditional risk factors are associated with accelerated atherosclerosis in HD patients, and increased AKW has been associated with various cardiovascular risk factors and atherosclerosis. In the current study, we aim to analyze various demographic, clinical, and laboratory parameters related to increased AKW in stable HD patients.
| Materials and Methods|| |
The subjects of this cross-sectional investigation included regular HD patients, who were clinically stable, and patients with normal renal function as the control group. This study was performed in accordance with the Declaration of Helsinki (http://www.wma.net/e/ policy/b3.htm), and written, informed consent was obtained from all patients before enrollment. The dialysis prescription in our study patients included four to five hours of HD, using a standard bicarbonate dialysis solution, thrice weekly, for all patients, with blood flow rates of 300-400 mL/minute. Urea kinetic modeling was performed to assess the delivered equilibrated dose of dialysis. Demographic characteristics including age, sex, body mass index (BMI), smoking status (smoker or non-smoker), and presence of diabetes mellitus (yes or no) and coronary artery disease (yes or no), were recorded for all patients. Coronary artery disease was defined as the presence of a previous myocardial infarction, angina pectoris or coronary revascularization procedure. All HD patients were virtually anuric and clinically euvolemic. Fasting blood samples were obtained before the start of the HD session, to determine the laboratory parameters, including, serum glucose, hemoglobin, white blood cell count, albumin, high sensitive C-reactive protein (hs-CRP), calcium and phosphorus, blood urea nitrogen (BUN) and creatinine, total cholesterol, high-density lipoprotein cholesterol (HDL-cholesterol), low-density lipoprotein cholesterol (LDL-cholesterol), triglycerides, and intact parathyroid hormone (i-P TH). Post-dialysis BUN levels, which were used to calculate the urea reduction ratio, were also measured in all HD patients. Post-dialysis, the posteroanterior (PA) chest radiographs were performed on all HD patients after the end of a dialysis session, when they had achieved their dry weight. Chest radiographs were also obtained for patients with normal renal function when they attended the clinic. An examiner, who was unaware of the result of the patient's measurements, reviewed the chest x-ray. The widest point of the ascending aortic knob was measured along the horizontal line from the point of the lateral edge of the trachea to the left lateral wall of the aortic knob [Figure 1].
|Figure 1: Method of aortic knob width measurements: The width of the aortic knob was measured from the point of the lateral edge of the trachea to the left lateral wall of the aortic knob|
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| Statistical Analysis|| |
Statistical analysis was performed using SPSS 15.0 (SPSS Inc, Evanston, Illinois, USA). Results were considered statistically significant if the two-tailed P value was less than 0.05. Data was checked for normality. For the comparison of laboratory parameters between HD patients and patients with normal renal function, the Student's t test and MannWhitney Test were used, as appropriate. The Pearson correlation coefficient was used for the correlation of increased AKW with other parameters. Stepwise Stepwise linear regression analysis was performed to analyze the independent factors related to increased AKW (as a dependent variable), both in the entire study group and in the HD group of patients.
| Results|| |
Initially, 108 HD patients were included. Two patients who experienced acute exacerbation of chronic obstructive lung disease, one patient with pneumonia, three patients with acute coronary syndrome in the previous month, two patients with decompensated heart failure and symptoms of hypervolemia, three patients with history of tuberculosis, and two patients with a history of mitral valve replacement were excluded. Additionally, we excluded four other patients whose chest x-ray was not properly centered (deviation of the trachea or shift of the mediastinum). The final patient population was composed of 91 patients. The etiologies of the end-stage renal disease (ESRD) included the following: Diabetes mellitus (n: 22), hypertension (n: 26), glomerulonephritis (n: 12), urolithiasis (n: 4), vesicoureteric reflux/pyelonephritis (n: 2), amyloidosis (n: 2), contrast nephropathy (n: 2), polycystic kidney disease (n: 1), and unknown (n: 20). A total of 65 patients with normal renal function were included as the control group. The demographic characteristics of the HD patients are shown in [Table 1]. The HD patients were not different with respect to age, gender, smoking status, presence of diabetes, and presence of cerebrovascular disease. However, the presence of coronary artery disease (27.5% vs. 6.2%, P: 0. 001) systolic BP (141.5 ± 19.1 mm Hg vs. 12 8.9 ± 14.1 mm Hg, P <0.0001), and diastolic BP (84.6 ± 13.5 mm Hg vs. 77.6 ± 7.4 mm Hg, P: 0.018) was higher, and the body mass index (BMI) was lower (23.6 ± 4.5 vs. 29.4 ± 5.4, P <0.0001) in HD patients compared to patients with normal renal function.
|Table 1: The baseline demographic characteristics of the 91 hemodialysis patients|
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The comparative clinical and laboratory parameters between HD patients and patients with normal renal function are shown in [Table 2].
|Table 2: The comparative laboratory data of hemodialysis patients and patients with normal renal function.|
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In the entire group, the Pearson correlation showed that increased AKW was correlated with age (r: 0.381, P <0.0001), systolic BP (r: 0.436, P <0.0001), creatinine (r: 0.494, P <0. 0001), BUN (r: 0.493, P <0.0001), albumin (r: -0.516, P <0.0001), uric acid (r: 0.333, P <0. 0001), phosphorus (r: 0.374, P <0.0001), i-PTH (r: 0.445, P <0.0001), HDL-cholesterol (r: -0.305, P <0.0001), triglyceride (r: 0.191, P: 0.017), and hs-CRP (r: 0.312, P <0.0001). In the HD patient group, the Pearson correlation showed that increased AKW correlated with age (r: 0.499, P <0.0001), BMI (r: 0.237, P: 0.024), pre-dialysis systolic BP (r: 0.364, P <0. 0001), hs-CRP (r: 0.310, P: 0.003), ferritin (r: -0.284, P: 0.006), and albumin (r: -0.401, P <0.0001).
In the entire group, stepwise linear regression of independent factors, including age, gender, being a dialysis patient, BMI, smoking status, presence of coronary artery disease, presence of diabetes mellitus, systolic and diastolic BP, total cholesterol, triglyceride, albumin, white blood cell count, hs-CRP, calcium, phosphorus, i-PTH, and the use of statins showed that age (B: 0.133, CI: 0.056-0.209, P: 0.001), male gender (B:3 .836, CI: 1.797-5.874, P <0.0001), dialysis treatment (B: 5.754, CI: 1.1 04-10.404, P: 0.016), systolic BP (B: 0.134, CI: 0.078-0.191, P <0.0001) and lower albumin levels (B: -3.524, CI: -6.506-(-0.542), P: 0.021) were independently associated with increased AKW.
Similarly, in the HD patients, stepwise linear regression of independent factors showed that age (P <0.0001), pre-dialysis systolic BP (P: 0.003), male gender (P <0.0001), being a non-smoker (P: 0.002), total cholesterol (P: 0.001), and i-PTH levels (P: 0.005) were independently associated with increased AKW [Table 3]. Presence of diabetes tended to be associated with increased AKW (P: 0.072).
|Table 3: Multivariate linear regression analysis of potential predictors of aortic knob width in hemodialysis patients|
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| Discussion|| |
To the best of our knowledge this is the first clinical study that has shown the association of AKW with various clinical and laboratory parameters in stable HD patients. In our center, all HD patients undergo routine chest x-ray at regular periods, even if they are asymptomatic. Measurement of AKW is an easy and simple process and provides valuable information. Indeed, increased AKW has been shown to be associated with hypertension, , kidney function, retinopathy, and left ventricular mass,  with vascular calcification,  arterial calcium content, coronary atherosclerosis, ,,, and even with subclinical atherosclerosis, without disease manifestation.  However, these studies have all been performed in patients without renal failure.
In the present study, we extended these findings and first showed the various parameters related to increased AKW. One of the findings of the present study was that increased age was associated with increased AKW.
This is not surprising, as the aorta undergoes marked changes with normal aging and these changes are due predominantly to alterations in the structural and physical properties of the arterial wall.  Wolak et al demonstrated that age is a major pathobiological determinant of aortic dilatation.  Thus, we speculate that in elderly dialysis patients the arterial wall undergoes structural alterations, which result in the increase of AKW. Pre-dialysis systolic BP was associated with increased AKW in the current study. It is known that in cases of longstanding hypertension (a condition highly prevalent in dialysis patients), aneurismal change of the aorta and dilatation of the aortic arch develops.  Indeed, various studies have shown the association of AKW with BP. ,, Rayner et al suggested that aortic dilatation is very much dependent on pressure.  Thus, we speculate that chronically elevated BP may result in aortic dilatation, which results in higher AKW. Male HD patients have a higher AKW when compared to female HD patients. Additionally, being male has been independently associated with increased AKD in our sample. It was found that diameters of both the ascending and descending aorta were higher in males compared with females.  Other studies also demonstrated that the male gender was associated with a larger aortic diameter. ,
Very interestingly and unexpectedly, being a non-smoker was associated with increased AKW in HD patients, but not in the whole population. It was demonstrated that smoking was an independent predictor only of the diameter of the descending aorta, but not the ascending aorta.  In another study, the percentage of smokers was significantly lower in the aortic knob calcification group than in the non-calcification group. However, there was no information regarding AKW and the smoking status in that study.  These conflicting results can be explained by the difference in the study population and obviously, further studies are needed to confirm the relationship of smoking and AKW.
Previous studies have revealed that calcification of the aorta was associated with serum markers of risk factors of atherosclerosis, such as, total cholesterol , and CRP.  Given the fact that the diameter of the ascending aorta was positively correlated with coronary artery calcification and was regarded as a representative marker of the generalized atherosclerotic process , and atherosclerosis was an inflammatory disease,  we incorporated total cholesterol, triglyceride, white blood cell count and Hs-CRP in our regression models. We found that only total cholesterol was independently associated with increased AKW, but only in the HD patients and not in the whole population. We believe that further studies are warranted regarding the relationship between CRP and AKW.
In dialysis patients, arterial stiffness, atherosclerosis, and vascular calcification are closely related. The presence of hyperphosphatemia, hyperparathyroidism, and hypercalcemia have been associated with vascular calcification, arterial stiffness, and atherosclerosis in HD patients. , As both atherosclerosis and aortic calcification are also related to increased AKW, we incorporated the i-PTH, calcium, and phosphorus levels in our regression model. Among these parameters, only i-PTH, but not calcium and phosphorus was associated with increased AKW in HD patients.
In the current study, although a trend exists, there was no independent association between increased AKW and the presence of diabetes in HD patients. It was demonstrated that diabetes was associated with an increased diameter of the ascending aorta.  Additionally, it was demonstrated that the aortic knob calcium was higher in diabetic patients compared to non-diabetics. , However, there was no detailed information regarding the AKW and presence of diabetes in these studies. The lack of association between the presence of diabetes and increased AKW in the current study could be explained by the small number of diabetic patients.
We are aware that our study has limitations that deserve mention. First, since our study has a cross-sectional design, the cause and effect relationships cannot be suggested. Second, our study sample is relatively small. Thus, our results must not be generalized to other patient populations, such as, peritoneal dialysis patients and chronic renal failure patients, not on dialysis. Third, we measured the variables only once, and thus, a temporal relationship cannot be suggested. It would be of interest to study whether a reduction of cardiovascular risk factors would also reduce AKW. Fourth, echo-cardiography was not performed routinely. However, in one study it was demonstrated that the aortic width measured by a chest radiograph correlated with the aortic root measurement on echocardiography supporting it as a reliable measurement of caliber for the thoracic aorta.  Besides, in most dialysis centers outside the hospitals, routine echocardiography was not readily available and there was a need for simple and inexpensive tests such as chest radiographs. Fifth, although the validity of AKW was demonstrated in normal patients, this issue had to be confirmed also in HD patients by comparing with the gold standard methods. Finally, it would be better to measure other variables such as. left ventricular hypertrophy and ejection fraction and its relationship with AKW.
In conclusion, various traditional and non-traditional risk factors are associated with increased AKW in HD patients. A chest x-ray is cheap, readily available, and can be evaluated by every physician easily. Therefore, assessment of AKW may be helpful in detecting asymptomatic HD patients with various cardio vascular risk factors. These preliminary findings may enhance the use of chest radiography as a screening method, and if confirmed, can assist risk stratification in HD patients.
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Dr. Baris Afsar
Department of Medicine, Division of Nephrology, Konya Numune State Hospital, Konya
[Table 1], [Table 2], [Table 3]