الفهرس 
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Abstract
End-stage renal disease has been a worldwide public health problem associated with increased
morbidity and mortality (Sarnak et al., 2003).
The mortality rate among patients with end stage renal disease (ESRD) who are undergoing dialysis
is approximately seven times greater than for similar individuals in the general population
and is largely attributed to cardiovascular causes (United States Renal Data System, 2011).
Cardiovascular diseases remain the leading cause of morbidity and mortality in patients with ESRD.
In ESRD patients, especially in those on dialysis therapy, the risk of cardiovascular death is
particularly high, 10– 20 times greater than in the general population (Pencak et al., 2013).
Identification of patients at high risk for cardiovascular disease and requiring aggressive
preventive and interventional strategies is an initial and essential step in managing patients with
hemodialysis. The Framingham Risk Score (FRS) is the most commonly used tool in clinical
settings to predict the coronary heart disease risk (CHD). The FRS allows clinicians to estimate
the patient‘s
10-year risk of coronary heart disease among individuals without a previous history of coronary
heart disease, stroke,
or peripheral vascular disease, by using traditional cardiac
risk factors including age, gender, systolic blood pressure, treatment of hypertension, total
cholesterol, HDL- cholesterol and cigarette smoking (Third report of the national cholesterol
education program (ncep) expert panel on detection, evaluation, and treatment of high
blood cholesterol in adults (adult treatment panel iii) final report, 2002).
In contrast to the situation in the general population, traditional risk factors cannot fully
explain the higher cardiovascular mortality in the ESRD population. One reason is that many
nontraditional risk factors for CVD, such as inflammation, endothelial dysfunction, oxidative
stress, vascular calcification, sympathetic overactivity, metabolic bone disease related to ESRD,
and protein– energy wasting, are more or less peculiar to the uremic milieu. Therefore, we need to
identify biomarkers that accurately reflect these risk factors in this specific patient population,
as the results provided in studies performed in the general population cannot automatically be
translated to the ESRD patient population (Go et al., 2004).
However, reverse epidemiology has been noted in hemodialysis (HD) patients in whom low blood
pressure and hypocholesterolemia predict high cardiovascular mortality (Levin et al., 2007).
Therefore, whether the clinical utility of FRS reliably
predicts cardiac death in hemodialysis patients remains unknown. The FRS is often considered the
reference standard but has limited accuracy, tending to over-estimate in low risk populations and
under-estimate in high risk populations.There is a number of noninvasive examinations that have
been proposed to improve risk prediction of cardiovascular diseases, including echocardiography,
ankle-brachial index (ABI) measurement, and pulse wave velocity (PWV) measurement (Chen et al.,
2012).
Evaluation of non-traditional factors may identify additional independent predictors of
coronary atherosclerosis that may further attenuate the association between ESRD and CVD and
represent novel mechanistic links in the development of atherosclerotic disease among patients with
ESRD (Baber et al., 2008).
Cardiovascular calcification is common in patients with ESRD and is an independent risk factor
that affects cardiovascular and all-cause mortality (Raggi et al., 2011).
Calcification is a pathologic process in the patients with end-stage renal disease that results in
a wide spectrum of pathological processes. Atherosclerosis risk factors in the normal population
are well known, but their role on uremic atherosclerosis is less studied. Other than dialysis
duration and age, there are other known risk factors for
calcification including elevated levels of parathormone (i-
PTH) and serum C-reactive protein (CRP), hyper- hemocysteinemia and reduction of serum
albumin. Although hyperphosphatemia and increased calcium intake accompanied by increasing calcium
phosphate product are important causes of calcification in ESRD patients, recent findings reveal
that inflammation also contributes to the development of calcification (Wang et al., 2009).
Echocardiography is a less expensive, widely available and non-radiation-based tool that could
prove useful in predicting the severity of vascular calcification in ESRD patients (Wang et al.,
2005).
As compared with patients without, patients who have ESRD and are receiving renal replacement
therapy have a higher prevalence of valvular calcification, including mitral annular
calcification (MAC), and aortic calcification (Varma et al., 2005).
Valvular calcification among dialysis patients is associated with subclinical measures of
atherosclerosis and is a powerful predictor of cardiovascular disease events and all-cause
mortality (Varma et al., 2005).
For many years, research on cardiovascular calcification in end stage renal disease (ESRD) has
focused on the role of hyperphosphatemia, high calcium phosphate product and hyperparathyroidism
(Cozzolino et al., 2001).
New insights in the calcification process have revealed
that vascular cells play an active, not only a passive role, as they stimulate osteoblastic
calcification differentiation of the vascular walls. A number of inhibitors of this
stimulation have been identified, including osteopontin, matrix Gla-protein and fetuin-A (Cozzolino
et al., 2005).
Fetuin-A, a 62-kD glycoprotein, is synthesized by liver cells and exists in the extracellular fluid
at a blood concentration of 0.5 to 1.0 g/l; it exerts strong inhibition of ectopic calcification by
inhibiting hydroxyapatite formation. Fetuin-A has been reported to be identified as a downregulated
in the presence of inflammation and related to the MIA (malnutrition, infl ammation, and
atherosclerosis) syndrome and the life expectancy of dialysis patients (Wang et al., 2005).
Fetuin-A binds to calcium phosphate forming soluble complexes with calcium and phosphate with
severe adherence and, therefore, acts as a buffer for serum calcium phosphate and potentially can
prevent calcification (Welsh et al., 2012).
Fetuin-A serum levels are significantly lower in ESRD patients with calcification than in other
ESRD patients (Ketteler et al., 2003).