Vascular calcification (VC) and arterial stiffness are associated with all-cause and cardiovascular (CV) mortality in the general and chronic kidney disease (CKD) populations, and screening methods to assess the degree of both could potentially be worthwhile in general clinical practice given the high prevalence and functional significance of these structural changes [1] [2] [3] . Arterial stiffness is an alteration of the arterial wall properties with multiple causes, some of which are old age, diabetes and hypertension. All these features of alteration of the arterial wall properties are highly prevalent in dialysis patients, and arterial stiffness is a common finding in this population. End-stage renal disease (ESRD) patients have stiffer arteries than age and blood pressure matching non uraemic subject [4] [5] .

The evaluation of the relationship between the radiological vascular calcification assessment and the measurement of vascular stiffness by pulse pressure (PP) is one of the KDIGO imaging Work Group research questions [6] . Vascular calcifications can be evaluated by ultrasonography and by plain X-ray through measurement of the simple vascular calcification score (SVCS) [7] [8] . Higher SVCS and PP were associated with higher mortality in this population. Simple and inexpensive methods are required to detect cardiovascular disease and to provide information that may be relevant for guiding therapeutic intervention in dialysis patients.

Vascular calcification rarely regresses the once developed, and therefore, ma- nagement involves prevention or diminishing the progression of existing VC. Determination of patients at the higher risk of CV morbidity and mortality may lead to alteration of medications to limit exogenous calcium exposure, stricter control of blood pressure and abnormalities in mineral metabolism, and changes in dialysis prescriptions (duration, frequency and dialysate), although there is a lack of current evidences to establish the optimal management for the problems of VC and arterial stiffness.

The present study was aiming at assessing vascular calcification by simple vascular calcification score based on plain radiographic films, and measurement of vascular stiffness by pulse pressure among patients with end-stage renal disease in the dialysis unit in Sohag University Hospital.

The study was conducted in the dialysis unit in Sohag University Hospital which included 250 patients on regular hemodialysis (HD). One hundred patients on regular HD, who fulfilled the inclusions criteria and accepted participation in this study, were included. The inclusions criteria included age > 18 years, regular hemodialysis for at least 12 months, and no previous history of parathyroidectomy. The included patients represented 40% of the patients on regular HD in the dialysis unit. Written informed consent was obtained from each patient and the study was approved from the ethic committee of our university. The patients underwent clinical evaluation including history taking, physical examination and measurement of body mass index (BMI) and measurement of the oral intake of calcium and calcitriol. At baseline, diagnosis of vascular disease was based on a query answered by the attending physicians, concerning previous clinical manifestations and test results, according to the usual standard of care.

Data was analyzed using STATA intercooled version 12.1. Quantitative data was represented as mean, standard deviation, median and range. Data was analyzed using student t-test to compare means of two groups. When the data was not normally distributed, Mann-Whitney test was used. Qualitative data was presented as number and percentage and compared using either Chi square test or fisher exact test. Univariate and multivariate logistic regression were used to calculate the odds ratios. P value was considered significant if it was less than 0.05.

Vascular calcifications in hemodialysis patients represent one of the factors contributing to the extremely high cardiovascular mortality for hemodialysis patients when compared with the general population. Vascular calcifications in those patients have already been related to arterial stiffness, cardiovascular disease and cardiovascular mortality [7] [9] . Diagnosis of vascular calcification is usually made with very expensive and highly technical devices like electron beam computed tomography or multislice computed tomography [10] . The use of simple and inexpensive methods such as the evaluation of PP or the assessment of the SVCS with plain X-ray has been suggested in the recent KDOQI clinical practice guidelines not for bone disease evaluation but for vascular calci-

SVCS; simple vascular calcification score, CI; confidence interval, Ca; calcium, P; phosphorous, PTH; parathyroid hormone.

fication assessment [11] .

Our study revealed that arterial stiffness assessment using PP is common among our studied patients on hemodialysis. There was significant association in multivariate analysis between higher PP and elevated systolic blood pressure. However, diastolic BP values showed no significant differences between patients in Group A and patients in Group B. These results are in agreement with results reported by Tozawa M et al. who demonstrated that the higher systolic blood

BP, lower diastolic BP and wider pulse pressure all confer greater CV and all- cause mortality risk [12] . Klassen PS et al. observed that the changes of arterial wall properties with age are associated with systolic BP increase and diastolic BP decrease. Increased Pulse pressure has been established as a cardiovascular disease risk factor in hemodialysis patients [13] . Presence of vascular disease was detected in 58 patients in our study and higher pulse pressure was associated with the presence of vascular disease in univariate analysis but not in multivariate analysis. London GM et al. observed that increased arterial stiffness could contribute to high pulse pressure [14] . Adragao T et al. found that PP was an independent predictor of peripheral arterial disease and significantly associated with cardiovascular morbidity and mortality in multivariate analysis in hemodialysis patients. And at baseline, clinical vascular disease was diagnosed in 36 patients (29%) and at the end of the follow-up vascular disease was detected in 61 patients (50%) [8] .

Univariate and multivariate analysis in our study showed that serum PTH was independently associated with higher PP while no association was detected with the higher PP and serum Ca or with serum P level. Our result was in agreement with that reported by Moe S. M. et al. and Blacher J. et al. which demonstrated that pulse pressure was independent of PTH values [15] [16] . However, they evaluated serum PTH level three evaluations per patient while in our study we evaluated serum PTH level once.

In our study, we found that higher pulse pressure was not correlated with hemodialysis duration and was not associated with age, sex, diabetes and BMI. Adragao T et al. demonstrated that PP was associated with diabetes and correlated with age [8] [17] . This could be explained by the differences in the number of studied population and the methods for the measurement of PP. Adragao T. et al. included 123 chronic hemodialysis patients with mean age 62.9 years and 20% were diabetic [8] . While our study included 100 patients with mean age 53.1 years and 5% were diabetic. We used pulse pressure only in the assessment of the arterial stiffness while other more reliable method can be used as evaluation of arterial stiffness by PWV by Adragao T. et al. who evaluated PWV twice, at baseline, 24 h after a HD session, using a non-invasive automated device, Complior [17] . In multivariate analysis, we found no correlation between higher pulse pressure and vascular calcification score. Adragao T. et al. reported that in all patients, using linear regression with the enter method and adjusting for multiple factors a higher vascular calcification score was directly associated with PP [17] .

In the present study, there was significant differences between higher and lower calcification score patients with regards to age, elevated BP and presence of vascular disease. And there was no significant difference between higher and lower score patients regarding gender, duration of dialysis and presence of DM. Elevated systolic BP was independently associated with vascular calcification while this independent association was not detected with age, gender, HD duration, and DM. Adragao T. et al. and Guerin A. P. et al. reported presence of significant differences between higher score and lower score patients with regards to age and HD duration [7] [8] . However, Guerin A. P. et al. reported no significant difference regarding to gender [7] . Adragao T. et al. reported significant difference regarding to DM, male sex and mean arterial pressure and these factor in addition to age were independently associated with vascular calcification [8] .

In the current study, vascular calcification score was not correlated with PTH values. This has already been demonstrated in other studies [7] [18] . Hyperphosphataemia and high calcium phosphate product are predictors of mortality in HD patients [19] . In our study, there was no correlation between calcium or phosphorus levels and vascular calcification. Andragao T. el al. reported that there was some evidence for a relationship between calcium or phosphorus levels and vascular disease: phosphorus levels were correlated with coronary artery disease and calcium levels were correlated with peripheral arterial disease. The final vascular calcification score was not correlated with calcium, phosphorus or iPTH levels, but calcium levels were correlated with the presence of iliac calcifications [8] . They showed that PTH levels were overestimated with the common intact parathormone (iPTH) assays because they detect not only PTH, but also evaluate C terminal fragments, which can have inhibitory activity. Similarly, Gue’rin et al. did not find any association between a semi-quantitative vascular calcification score evaluated by B-mode ultrasonography and calcium, phospho- rus and iPTH levels [7] . London et al. found a link between low bone turnover and VC with a study showing that a high arterial calcification score was associated with bone histomorphometry suggestive of low bone activity and adynamic bone disease, indicating that over-suppression of PTH may also influence the development of VC [20] . Therefore, both high and low PTH levels are associated with CV events and mortality and vascular calcification.

The present study has some limitations. Firstly, there were a relatively small number of patients conducted in a single institution. Including patients from other institutions could have a positive impact on the results. However, adding patients from other dialysis units has some socioeconomic difficulties and needs a complicated administrative process. Secondly, another limitation of this study was a selection bias in the subjects. All patients were ESRD on hemodialysis for 12 months or more, 54% had history of hypertension and 58% were previously diagnosed to have vascular disease. So, the result of this study might be limited to apply for subjects with less advances chronic renal diseases and in those without hypertension or clinical evidence of vascular diseases. Thirdly, we did not compare assessment of vascular calcification and arterial stiffness by using SVCS and PP with other imaging modalities such as electron beam computed tomography, B-mode ultrasonography and PWV with Complior due to high cost of these investigations. Fourthly, pulse pressure was evaluated once a month during the same 6 months period and the serum levels of Ca, P and PTH were measured once due to high cost of these investigations. Finally, vascular calcification score is not quantitative and therefore is not adequate for accurately assessing the progression of calcifications, as opposed to the scores evaluated by electron beam computed tomography. Further larger prospective studies were needed to determine the optimal methods for assessment of vascular diseases in ESRD patients.

In conclusion, arterial stiffness and vascular calcifications are common in patients with ESRD on regular hemodialysis. PP and SVCS are simple and inexpensive methods for assessment of vascular calcifications and arterial stiffness in hemodialysis patients. Therefore, they can be used to detect the risk of cardiovascular disease and to provide important information that may guide the manage- ment of hemodialysis patients.

Elsamman, M.K., Ezzat, M.A.W., Mohammad, M.I., Mostafa, R.G. and Hassan, A.T.A. (2017) Assessment of Arterial Stiffening and Vascular Calcifications in End-Stage Renal Disease Patients. World Journal of Cardiovascular Diseases, 7, 131-143. https://doi.org/10.4236/wjcd.2017.74013