Sclerostin, cardiovascular disease and mortality: a systematic review and meta-analysis

Int Urol Nephrol. 2016 Dec;48(12):2029-2042. doi: 10.1007/s11255-016-1387-8. Epub 2016 Aug 6.

Abstract

Background and aim: 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.

Materials and 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 χ 2 = 12.24, I 2 = 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 χ 2 = 10.74, I 2 = 91 %, p = 0.001).

Conclusion: 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.

Keywords: Cardiovascular event; Chronic kidney disease; Sclerostin.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Bone Morphogenetic Proteins / metabolism*
  • Cardiovascular Diseases / mortality*
  • Chronic Kidney Disease-Mineral and Bone Disorder* / epidemiology
  • Chronic Kidney Disease-Mineral and Bone Disorder* / metabolism
  • Genetic Markers
  • Humans
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Vascular Calcification* / epidemiology
  • Vascular Calcification* / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Bone Morphogenetic Proteins
  • Genetic Markers
  • SOST protein, human