High TMAO Levels Predict Abdominal Aortic Aneurysm Progression and Surgical Risk: JAMA
USA: A study published in JAMA Cardiology has found that circulating levels of trimethylamine N-oxide (TMAO), a metabolite produced by gut microbiota, may serve as an important biomarker in predicting the risk of abdominal aortic aneurysms (AAA), their growth rate, and the likelihood of surgical intervention.
The research, led by Dr. Scott J. Cameron from the Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, analyzed whether TMAO levels could help identify patients at heightened risk for aneurysm-related complications.
The prospective study included two independent clinical cohorts: 237 patients in Uppsala, Sweden, and 658 patients in Cleveland, Ohio. All participants underwent serial aortic imaging and long-term monitoring, while plasma TMAO concentrations were measured using advanced mass spectrometry techniques.
The following were the key findings of the study:
- Elevated TMAO levels showed a consistent and significant association with abdominal aortic aneurysm outcomes.
- In the European cohort, higher TMAO was linked to a 2.75-fold greater risk of rapid aneurysm growth and a 2.67-fold higher likelihood of surgical recommendation.
- In the US cohort, elevated TMAO corresponded to a 2.71-fold increased risk of fast-growing aneurysms and a 2.73-fold higher chance of surgery.
- Combined analysis of both cohorts confirmed more than double the adjusted risk for both accelerated aneurysm progression and surgical need.
- Incorporating TMAO levels into cardiovascular risk models improved prediction accuracy for aneurysm growth and surgical requirement.
- The findings suggest that individuals with elevated TMAO may benefit from closer surveillance and earlier intervention to prevent rupture or dissection.
The study also pointed out certain limitations. Family history of aneurysms and connective tissue disorders were not included in the US data, while dietary information was unavailable in both cohorts. Additionally, TMAO was measured only once at baseline, leaving it unclear whether serial monitoring might provide greater prognostic value. Despite these constraints, the association between TMAO and AAA progression remained robust across both populations and different health care settings.
The researchers highlighted that current treatment options for AAA are limited to surgical repair, with no effective medical therapies to slow disease progression. Given that previous animal studies have shown that targeting TMAO production can block aneurysm growth and rupture, these findings open the possibility of developing gut microbiota–based therapeutic approaches. They concluded that prospective interventional studies are now essential to confirm whether lowering TMAO can effectively reduce aneurysm growth rates and delay the need for surgery.
Reference:
Cameron SJ, Li XS, Benson TW, et al. Circulating Trimethylamine N-Oxide and Growth Rate of Abdominal Aortic Aneurysms and Surgical Risk. JAMA Cardiol. Published online August 20, 2025. doi:10.1001/jamacardio.2025.2698
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