Article Impact Level: HIGH Data Quality: STRONG Summary of JAMA Cardiology. https://doi.org/10.1001/jamacardio.2025.2698 Dr. Scott J. Cameron et al.
Points
- Elevated circulating levels of the gut metabolite TMAO were significantly associated with an increased risk of developing an abdominal aortic aneurysm in two large independent patient cohorts.
- This study showed that high TMAO levels could successfully identify individuals at a heightened risk for faster aneurysm growth, defined as expansion of 4.0 mm or more per year.
- Patients with elevated TMAO were also found to have a significantly greater likelihood of meeting the established criteria for recommended surgical intervention to repair their abdominal aortic aneurysm.
- The addition of TMAO measurements to existing models containing traditional risk factors significantly improves the ability to predict adverse aneurysm outcomes, such as rapid growth and the need for surgery.
- These findings suggest that diet plays an important role, as TMAO is generated by gut microbes from nutrients abundant in red meat and other animal products.
Summary
A prospective cohort study investigated whether the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) is associated with abdominal aortic aneurysm (AAA) risk and progression. The study analyzed two independent cohorts undergoing aortic imaging surveillance: a European cohort of 237 individuals (median age 65; 89.0% male) and a US cohort of 658 individuals (median age 63; 79.5% male). In both populations, elevated plasma TMAO concentrations were significantly associated with AAA risk, independent of traditional cardiovascular risk factors and kidney function.
The findings demonstrated a consistent and significant link between elevated TMAO and adverse AAA outcomes. In the European cohort, higher TMAO predicted greater risk for fast-growing AAA (adjusted odds ratio [aOR], 2.75; 95% CI, 1.20-6.79) and recommended surgical intervention (aOR, 2.67; 95% CI, 1.24-6.09). These results were replicated in the US cohort, which showed a similar heightened risk for rapid AAA growth (aOR, 2.71; 95% CI, 1.53-4.80) and surgical recommendation (aOR, 2.73; 95% CI, 1.56-4.80).
The study concluded that adding TMAO to base models with traditional risk factors significantly improved risk estimation for both the rapid expansion of AAA and the need for surgical intervention. The results suggest that circulating TMAO is a promising biomarker for identifying high-risk AAA patients. This could aid in clinical decision-making by helping to select individuals who may benefit from more frequent surveillance imaging or earlier consideration for surgical repair to prevent aortic dissection or rupture.
Link to the article: https://jamanetwork.com/journals/jamacardiology/article-abstract/2837610
References Cameron, S. J., Li, X. S., Benson, T. W., Conrad, K. A., Wang, Z., Fleifil, S., Maegdefessel, L., Mani, K., Björck, M., Scalise, A., Pham, M., Shim, S., Wanhainen, A., Sharew, B., Tian, M. Y., Wu, Y., Lusis, A. J., Lyden, S. P., Tang, W. H. W., … Hazen, S. L. (2025). Circulating trimethylamine n -oxide and growth rate of abdominal aortic aneurysms and surgical risk. JAMA Cardiology. https://doi.org/10.1001/jamacardio.2025.2698
