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Sclerostin, cardiovascular disease and mortality: a systematic review and meta-analysis
Mehmet Kanbay1, Yalcin Solak2, Dimitrie Siriopol3
1Division of Nephrology, Department of Medicine, Koc University School of Medicine, Sariyer, Istanbul, Turkey. mkanbay@ku.edu.tr.
Insights
Serum sclerostin levels are not significantly associated with all-cause or cardiovascular mortality in patients with chronic kidney disease mineral and bone disorder (CKD-MBD). This systematic review and meta-analysis found no link between sclerostin and mortality risk in CKD patients.
Area of Science:
- Nephrology
- Endocrinology
- Cardiovascular Medicine
Background:
- Chronic kidney disease mineral and bone disorder (CKD-MBD) is linked to higher illness and death rates.
- Previous studies suggest a connection between sclerostin levels, mortality, and vascular calcification in CKD patients.
Purpose of the Study:
- To systematically review and meta-analyze the effect of sclerostin on cardiovascular events (CVE), all-cause mortality, cardiovascular mortality, and vascular calcification in CKD patients.
- To determine the association between serum sclerostin levels and the risk of fatal and nonfatal CVE and all-cause mortality.
Main Methods:
- A comprehensive literature search was conducted across major electronic databases (Medline, PubMed, EMBASE, Web of Science).
- Hazard ratios from nine observational prospective studies involving 1788 patients were pooled using a random-effects model.
- Statistical significance was determined using the z test (p < 0.05).
Main Results:
- Analysis of three studies (503 patients) indicated no significant association between sclerostin levels and all-cause mortality risk (HR = 1.01, p = 0.16).
- Two studies (412 patients) showed no significant association between sclerostin levels and cardiovascular mortality risk (HR = 1.03, p = 0.17).
- Significant heterogeneity was observed in both all-cause and cardiovascular mortality analyses.
Conclusions:
- Despite study limitations including small size and heterogeneity, serum sclerostin levels were not found to be associated with all-cause or cardiovascular mortality in the studied CKD patient cohort.
- Further research may be needed to clarify the role of sclerostin in CKD-MBD and its potential impact on cardiovascular outcomes.
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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