1. Frailty and risk of systemic atherosclerosis: A bidirectional Mendelian randomization study.
- Author
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Xu, Liugang, Wang, Yajun, Ji, Hongyun, Du, Wei, You, Chunhui, Chen, Jin, Jiang, Jianyu, Shan, Yisi, Pan, Qian, and Cao, Ruihong
- Subjects
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ATHEROSCLEROSIS , *HIGH density lipoproteins , *PERIPHERAL vascular diseases , *GENOME-wide association studies , *FRAILTY , *SYSTEMIC risk (Finance) - Abstract
Background: Numerous observational studies have reported an association between frailty and atherosclerosis. However, the causal relationship between frailty and the occurrence of atherosclerosis in different anatomical sites remains unclear. we conducted a bidirectional Mendelian randomization (MR) study to evaluate the causal relationship between the frailty index (FI), and both systemic atherosclerosis and lipids. Methods: We obtained summary statistics from large-scale genome-wide association studies (GWAS) of various phenotypes, including frailty (n = 175,226), coronary atherosclerosis (n = 56,685), cerebral atherosclerosis (n = 150,765), peripheral arterial disease (PAD) (n = 361,194), atherosclerosis at other sites (n = 17,832), LDL-C (n = 201,678), HDL-C (n = 77,409), and triglycerides (n = 78,700). The primary MR analysis employed the inverse variance weighted (IVW) method. Furthermore, to assess reverse causality, we employed inverse MR and multivariate MR analysis. Results: Genetically predicted FI showed positive associations with the risk of coronary atherosclerosis (OR = 1.47, 95% CI 1.12–1.93) and cerebral atherosclerosis (OR = 1.99, 95% CI 1.05–3.78), with no significant association (p >0.05) applied to peripheral arterial disease and atherosclerosis at other sites. Genetically predicted FI was positively associated with the risk of triglycerides (OR = 1.31, 95% CI 1.08–1.59), negatively associated with the risk of LDL-C (OR = 0.87, 95% CI 0.78–0.97), and showed no significant association with the risk of HDL-C (p >0.05). Furthermore, both reverse MR and multivariate MR analyses demonstrated a correlation between systemic atherosclerosis, lipids, and increased FI. Conclusion: Our study elucidated that genetically predicted FI is associated with the risk of coronary atherosclerosis and cerebral atherosclerosis by the MR analysis method, and they have a bidirectional causal relationship. Moreover, genetically predicted FI was causally associated with triglyceride and LDL-C levels. Further understanding of this association is crucial for optimizing medical practice and care models specifically tailored to frail populations. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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