A cohort study conducted in Europe and the United States demonstrated an association between elevated blood levels of trimethylamine N-oxide (TMAO)—a metabolite produced in the presence of the gut microbiota—and an increased risk of progression of abdominal aortic aneurysm (AAA). The findings, which may enable more precise identification of patients with rapidly expanding AAAs or those requiring surgical intervention, were published in JAMA Cardiology.
Abdominal aortic aneurysm affects millions of patients annually. Currently, effective treatment options are limited to surgical repair or endovascular intervention. In preclinical models, therapeutic targeting of TMAO has been shown to counteract AAA progression and rupture.
In humans, risk factors for AAA progression include male sex, advanced age, smoking, hypertension, and atherosclerosis. However, a biomarker capable of predicting rapid AAA growth or the need for surgical intervention is lacking. The present cohort study evaluated whether circulating TMAO levels could serve as such a biomarker. The authors built on more than a decade of research into the role of the gut microbiome in cardiovascular health, including the effects of TMAO.
This prospective study included 895 adults undergoing serial imaging examinations of the abdominal aorta (measurement of subrenal diameter), in whom serum TMAO levels were assessed. Two independent cohorts were analyzed: a European cohort consisting of individuals examined in Uppsala, Sweden (n = 237), and a U.S. cohort of patients examined at the Cleveland Clinic in Ohio (n = 658). The median age was 65 years in the European cohort and 63 years in the U.S. cohort, with the majority of participants being male (89% in the European cohort and 79.5% in the U.S. cohort).
TMAO plasma concentrations were measured using stable isotope dilution liquid chromatography–tandem mass spectrometry. The association between TMAO levels and AAA risk was evaluated, with AAA risk defined as rapid growth (≥ 4.0 mm/year) or recommendation for surgical repair (rapid AAA growth or AAA diameter ≥ 55 mm).
In the European cohort, elevated circulating TMAO levels were significantly associated with AAA risk independently of traditional risk factors and kidney function. Higher TMAO levels predicted both an increased risk of rapidly growing AAA (adjusted odds ratio [aOR] 2.75; 95% CI 1.20–6.79) and recommendation for surgical intervention (aOR 2.67; 95% CI 1.24–6.09).
Similar results were observed in the U.S. cohort and in the combined European and U.S. cohort. Elevated TMAO levels predicted a significantly higher risk of rapid AAA growth (U.S. cohort: aOR 2.71; 95% CI 1.53–4.80; combined cohort: aOR 2.30; 95% CI 1.47–3.62) and recommendation for surgical repair (U.S. cohort: aOR 2.73; 95% CI 1.56–4.80; combined cohort: aOR 2.41; 95% CI 1.55–3.74).
Adding TMAO to models that included traditional cardiovascular risk factors significantly improved the prediction of both rapid AAA growth and the need for surgical intervention.
TMAO may play a role in the development, progression, and severity of abdominal aortic aneurysm. It has the potential to serve as a biomarker to help identify patients who may benefit from closer surveillance and timely surgical intervention to prevent dissection or rupture of the abdominal aorta.
Editorial Team, Medscope.pro
Sources:
1. Cameron S. J., Li X. S., Benson T. W. et al. Circulating Trimethylamine N-Oxide and Growth Rate of Abdominal Aortic Aneurysms and Surgical Risk. JAMA Cardiology, August 20, 2025, doi: 10.1001/jamacardio.2025.2698.
2. New Cleveland Clinic research identifies link between gut microbes and an elevated risk for abdominal aortic aneurysms. Press release, Cleveland Clinic, August 20, 2025. Available at: https://newsroom.clevelandclinic.org/2025/08/20/new-cleveland-clinic-research-identifies-link-between-gut-microbes-and-an-elevated-risk-for-abdominal-aortic-aneurysms
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