title: Sclerostin, cardiovascular disease and mortality: a systematic review and meta-analysis.
abstract: OBJECTIVE
  Chronic kidney disease mineral and bone disorder (CKD-MBD) is associated with increased morbidity and mortality. Several cross-sectional studies investigated the association of serum sclerostin levels with mortality and vascular calcification. We aimed to investigate the effect of sclerostin on cardiovascular events (CVE), all-cause/cardiovascular mortality and vascular calcification in patients with CKD through systematic review and meta-analysis. The primary outcome was the association between sclerostin level and development of fatal and nonfatal CVE and all-cause mortality.
  
  
  METHODS
  A literature search was performed using electronic databases Medline Ovid/Medline, PubMed/Medline, EMBASE and ISI Web of Science. Extracted hazard ratios from the included study protocols were pooled separately using the random-effects model (DerSimonian Laird). The equivalent z test was performed for each pooled HR, and if p < 0.05 it was considered statistically significant.
  
  
  RESULTS
  In our final analysis, we included nine observational prospective studies involving 1788 patients (minimum 91 and maximum 673 patients). For the all-cause mortality, three studies with 503 patients showed that sclerostin levels were not significantly associated with all-cause mortality risk (HR = 1.01, 95 % CI 0.99-1.03, p = 0.16; heterogeneity χ2= 12.24, I2= 84 %, p = 0.002). For cardiovascular mortality, two studies with 412 patients showed that sclerostin levels were not significantly associated with cardiovascular mortality risk (HR = 1.03, 95 % CI 0.99-1.07, p = 0.17; heterogeneity χ2= 10.74, I2= 91 %, p = 0.001).
  
  
  CONCLUSIONS
  Although the studies are mostly small in size, heterogeneous and have conflicting results, we have demonstrated that serum sclerostin levels were not associated with all-cause and cardiovascular mortality.
authors: Division of Nephrology, Department of Medicine, Koc University School of Medicine, Sariyer, Istanbul, Turkey. mkanbay@ku.edu.tr.
authors: Mehmet
authors: http://orcid.org/0000-0002-1297-0675
authors: M
authors: Kanbay
authors: Department of Nephrology, Sakarya Training and Research Hospital, Sakarya, Turkey.
authors: Yalcin
authors: Y
authors: Solak
authors: Nephrology Department, "Gr. T. Popa" University of Medicine and Pharmacy, Iasi, Romania.
authors: Dimitrie
authors: D
authors: Siriopol
authors: Department of Cardiology, Koc University Hospital, Istanbul, Turkey.
authors: Gamze
authors: G
authors: Aslan
authors: Division of Nephrology, Department of Medicine, Konya Numune State Hospital, Konya, Turkey.
authors: Baris
authors: B
authors: Afsar
authors: Division of Endocrinology, Department of Medicine, Koc University School of Medicine, Istanbul, Turkey.
authors: Dilek
authors: D
authors: Yazici
authors: Nephrology Department, "Gr. T. Popa" University of Medicine and Pharmacy, Iasi, Romania.
authors: Adrian
authors: A
authors: Covic
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000401:mortality*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000453:epidemiology / Q000378:metabolism; D005819:Genetic Markers; D006801:Humans; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D061205:Vascular Calcification / Q000453:epidemiology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human
keywords: Cardiovascular event; Chronic kidney disease; Sclerostin