Serum metabolites and risk of aortic dissection: a two-sample Mendelian randomization study.

Purpose: Acute aortic dissection is a serious cardiovascular emergency with a high mortality rate. Its pathogenesis is complex and remains unclear. This study aimed to assess the connection between the levels of genetically predicted circulating metabolites and the risk of aortic dissection.

Methods: A two-sample Mendelian randomization (MR) approach was employed to determine the causal relationship between genetically determined metabolites and the incidence of aortic dissection. In total, 1091 specific metabolites were identified from genome-wide association study (GWAS) data and aortic dissection involving 207,011 participants. Causal inference was performed using the inverse-variance weighted (IVW) method, supplemented by extensive sensitivity analyses to ensure the validity of the results. In addition, pathway analysis was performed using the Metaconflict 5.0 platform.

Results: We found that six serum metabolites were genetically associated with an increased risk of aortic dissection, whereas eleven metabolites were associated with a decreased risk, and these associations were confirmed by rigorous sensitivity analyses. Reverse MR analysis indicated that aortic dissection could decrease the serum level of kynurenine (odds ratio (OR) = 0.9675, 95% confidence interval (CI) 0.9383-0.9976,  = 0.0344). The metabolic pathways suggested that steroid hormone biosynthesis, steroidogenesis, and bile acid biosynthesis are involved in the pathogenesis of aortic dissection.

Conclusion: This MR analysis revealed a significant association between seventeen serum metabolites and the risk of aortic dissection. Further research is needed to fully elucidate the complex mechanisms underlying these associations.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-024-01807-5.