The cause-effect relationship between sclerostin levels, cardiovascular biomarkers, risk factors, and cardiovascular disease
Abstract Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to study the effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans. Public GWAS were used for study outcomes, with findings validated using UK Biobank patient-level data including biomarkers. Lower sclerostin levels were associated with higher bone density and 75% reduction in hip fracture risk. However, reduced sclerostin led to 50-70% excess coronary artery disease risk, 30% to 80% increased risk of myocardial infarction, 50% to 70% increased risk of type 2 diabetes, and with worse cardiovascular biomarkers, including higher glucose, LDL cholesterol, apolipoprotein B and triglycerides, and decreased HDL cholesterol and lipoprotein A levels. We provide genetic evidence of a causal association between reduced levels of sclerostin and improved bone health and fracture protection, but increased cardiovascular events and risk factors..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
ResearchSquare.com - (2023) vom: 31. Juli Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Prieto-Alhambra, Daniel [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-3209943/v1 |
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| 520 | |a Abstract Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to study the effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans. Public GWAS were used for study outcomes, with findings validated using UK Biobank patient-level data including biomarkers. Lower sclerostin levels were associated with higher bone density and 75% reduction in hip fracture risk. However, reduced sclerostin led to 50-70% excess coronary artery disease risk, 30% to 80% increased risk of myocardial infarction, 50% to 70% increased risk of type 2 diabetes, and with worse cardiovascular biomarkers, including higher glucose, LDL cholesterol, apolipoprotein B and triglycerides, and decreased HDL cholesterol and lipoprotein A levels. We provide genetic evidence of a causal association between reduced levels of sclerostin and improved bone health and fracture protection, but increased cardiovascular events and risk factors. | ||
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