Association of Circulating Sclerostin Levels with Carotid Artery Atherosclerosis and Endothelial Function in Prevalent Haemodialysis Patients

Abstract

Atherosclerosis plays a key role in the pathogenesis of cardiovascular diseases which are the major causes of death in hemodialysis patients. Increased risk of atherosclerosis thus cardiovascular diseases in hemodialysis patients is attributed to nontraditional risk factors in addition to traditional risk factors (Stenvinkel et al., 2003; Muntner et al., 2004). Sclerostin has emerged as a novel regulator of bone metabolism. This 22.5 kDa protein is synthesized in osteocytes and is a potent down-regulator of bone metabolism by reducing osteoblast differentiation and function via canonical Wnt-signalling inhibition. Recent studies suggested that serum sclerostin may have a potential role in atherosclerosis. Canonical Wnt-signalling and accompanying β-catenin activation have been shown to be pro-proliferative in arterial and venous SMCs, both in vitro and in vivo. Increased SMC proliferation and migration entirely change the composition and structure of the blood vessel wall, leading to atherosclerosis (Mill and George, 2012). As an inhibitor of canonical Wnt-signalling, we can speculate that sclerostin may be associated with atherosclerosis. High serum sclerostin was described in patients with CKD (Brandenburg et al., 2013) so it may have a role in accelerated atherosclerosis in those patients. This study was conducted to investigate the relationship between circulating sclerostin and carotid artery atherosclerosis and endothelial function in hemodialysis patients. Impaired endothelial function is the early functional surrogate marker of atherosclerosis. This study comprised 90 hemodialysis patients receiving three hemodialysis sessions weekly in Ain Shams University hospital dialysis unit. Demographic data, medical history, clinical parameters, dialysis treatment parameters, prescribed medications were recorded. Laboratory parameters including serum sclerostin level were measured. Ultrasound was used to assess carotid artery atherosclerosis and brachial artery FMD as a surrogate for endothelial function. Sclerostin level of study population was (2.21 ± 0.77 ng/ml) which is higher than levels observed in general populations (Durosier et al., 2013; Yamamoto et al., 2013). Serum PTH and brachial artery FMD were independently associated with serum sclerostin levels. In addition it was significantly associated with age, serum calcium, CRP, AACs, CIMT in univariate analysis. Serum sclerostin was found to be associated with caro