Genetic proxy of lipid-lowering drugs and calcific aortic valve stenosis: A Mendelian randomization study.
Heliyon
; 10(13): e34089, 2024 Jul 15.
Article
in En
| MEDLINE
| ID: mdl-39055828
ABSTRACT
Background:
Lipid metabolism plays an important role in the pathogenesis and development of calcific aortic valve stenosis. Our aim was to evaluate the causal effect of lipid-lowering drugs, such as low-density lipoprotein cholesterol (LDL-C) lowering and triglyceride lowering drugs, on the outcome of aortic valve stenosis using a two-sample Mendelian randomization (MR) study.Methods:
We used two genetic tools to represent the exposure of lipid-lowering drugs, including expression quantitative trait loci for the expression of drug target genes, and genetic variants within or near drug target genes that are associated with LDL-C and triglyceride concentrations from Genome-Wide Association Studies (GWAS). Effect estimates were calculated using summary-data-based MR (SMR) and inverse-variance-weighted MR (IVW-MR) analysis.Results:
Based on the results of SMR and IVW-MR analysis, LDL-C-lowering PCSK9 inhibitors have potential in reducing the risk of aortic valve stenosis (for SMR, OR 1.044; 95%CI 1.002-1.404; P = 0.047; for IVW-MR, OR 1.647, 95%CI 1.316-2.062, P < 0.001). However, no significant association was observed between triglyceride target gene expression, as well as triglyceride-lowering drugs, and aortic valve stenosis.Conclusion:
This two-sample drug-targeted MR study suggests a potential causal relationship between PCSK9 inhibitors and the reduction of calcific aortic valve stenosis risk.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Heliyon
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
United kingdom