The potential protective effect of 3-Hydroxybutyrate against aortic dissection: a mendelian randomization analysis

Background: 3-Hydroxybutyrate, also called β-hydroxybutyrate, is a significant constituent of ketone bodies. Previous observational and experimental studies have suggested that ketogenic diet, especially 3-hydroxybutyrate, may have a protective effect against cardiovascular disease. However, the relationship between ketone bodies, especially 3-hydroxybutyrate, and aortic dissection remains uncertain.

Materials and methods: Publicly accessible data from genome-wide association study (GWAS) was utilized to obtain information on ketone bodies, including 3-hydroxybutyrate, acetoacetate and acetone as exposure respectively, while GWAS data on aortic dissection was used as outcome. Subsequently, two-sample Mendelian randomization (MR) analysis was conducted to examine the potential relationship between ketone bodies and aortic dissection. Then, reverse and multivariate Mendelian randomization analyses were performed. Additionally, sensitivity tests were conducted to assess the robustness of MR study.

Results: The inverse-variance weighted (IVW) method of Mendelian randomization analysis of gene prediction observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection (OR 0.147, 95% CI 0.053-0.410). Furthermore, consistent findings were obtained through the implementation of the weighted median, simple mode, Mendelian randomization-Egger (MR-Egger), and weighted mode methods. After adjusting acetoacetate (OR 0.143, 95% CI 0.023-0.900) or acetone (OR 0.100, 95% CI 0.025-0.398), MR analysis of gene prediction still observed a negative correlation between 3-hydroxybutyrate and risk of aortic dissection. No indications of heterogeneity or pleiotropy among the SNPs were detected.

Conclusion: The findings from the MR analysis demonstrated that genetically predicted 3-hydroxybutyrate exhibits a protective effect against aortic dissection.