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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). |