Genetic proxy of lipid-lowering drugs and calcific aortic valve stenosis: A Mendelian randomization study
Yucheng Hou,
Jingwei Zhao,
Wanchuang Xu,
Lei Chen,
Jingyue Yang,
Ziheng Wang,
Ke Si
Affiliations
Yucheng Hou
Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
Jingwei Zhao
Department of General Surgery, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine & Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, China
Wanchuang Xu
Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China; Suzhou Medical College, Soochow University, Suzhou, China
Lei Chen
Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China
Jingyue Yang
Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China; Suzhou Medical College, Soochow University, Suzhou, China
Ziheng Wang
MOE Frontier Science Centre for Precision Oncology, University of Macau, Macau SAR, China; The School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia; Suzhou Industrial Park Monash Research Institute of Science and Technology, Suzhou, China; Corresponding author.MOE Frontier Science Centre for Precision Oncology, University of Macau, SAR Macau, China.
Ke Si
Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China; Corresponding author. Department of Cardiovascular Surgery, The First Affiliated Hospital of Soochow University, No.899, Pinghai Road, Suzhou, China.
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.
