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

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.

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Correspondence to Mehmet Kanbay.

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Kanbay, M., Solak, Y., Siriopol, D. et al. Sclerostin, cardiovascular disease and mortality: a systematic review and meta-analysis. Int Urol Nephrol 48, 2029–2042 (2016). https://doi.org/10.1007/s11255-016-1387-8

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Keywords

  • Sclerostin
  • Cardiovascular event
  • Chronic kidney disease