{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T18:52:14Z","timestamp":1789930334574,"version":"4.0.1"},"reference-count":49,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:sec id=\"ab-hoi250041-4\"><jats:title>Importance<\/jats:title><jats:p>Plasma levels of the gut microbiota\u2013dependent metabolite trimethylamine <jats:italic>N<\/jats:italic>-oxide (TMAO) are associated with prevalent abdominal aortic aneurysms (AAA) in humans and fostering of AAA progression in animal models; therapeutic targeting of TMAO production blocks AAA progression and rupture in multiple mouse models. A blood biomarker that identifies individuals at risk for incident AAA development, accelerated AAA expansion, or recommendation for surgical AAA repair could be an asset for risk stratification.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250041-5\"><jats:title>Objective<\/jats:title><jats:p>To determine whether TMAO is associated with risk for AAA development, rapid AAA expansion, and risk for recommended surgical intervention.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250041-6\"><jats:title>Design, Setting, and Participants<\/jats:title><jats:p>This was a prospective cohort study using 2 independent clinical cohorts undergoing aorta imaging surveillance: a European cohort and a US cohort. Included in this study were patients undergoing serial imaging surveillance of the aorta and long-term outcome monitoring. Patients were recruited from single-center studies in Uppsala, Sweden, and Cleveland, Ohio. Study data were analyzed from October 2023 to May 2025.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250041-7\"><jats:title>Exposures<\/jats:title><jats:p>Plasma TMAO concentrations measured by stable isotope dilution liquid chromatography with tandem mass spectrometry.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250041-8\"><jats:title>Main Outcomes and Measures<\/jats:title><jats:p>The association of TMAO levels with AAA risk, fast-growing AAA (\u22654.0 mm per year), and recommended surgical intervention (\u22654.0 mm per year or \u22655.5 cm diameter).<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250041-9\"><jats:title>Results<\/jats:title><jats:p>The European cohort included 237 individuals (median [IQR] age, 65 [65-73] years; 211 male [89.0%]), and the US cohort included 658 individuals (median [IQR] age, 63 [57-70] years; 523 male [79.5%]). In the European cohort, elevated circulating TMAO was significantly associated with AAA risk independent of traditional risk factors and kidney function. Moreover, elevated TMAO predicted both 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). Similar patterns were observed in the US cohort and the combined European and US cohort, with heightened circulating TMAO corresponding with significantly increased adjusted risk for fast-growing AAA (US cohort: aOR, 2.71; 95% CI, 1.53-4.80; combined cohort: aOR, 2.30; 95% CI, 1.47-3.62) and recommended surgical intervention (US cohort: aOR, 2.73; 95% CI, 1.56-4.80; combined cohort: aOR, 2.41; 95% CI, 1.55-3.74). Addition of TMAO to base models containing traditional cardiovascular risk factors resulted in significant improvement in both risk estimation for fast-growing AAA and predicting recommended surgical intervention.<\/jats:p><\/jats:sec><jats:sec id=\"ab-hoi250041-10\"><jats:title>Conclusion and Relevance<\/jats:title><jats:p>Results of this cohort study suggest that elevated circulating TMAO levels were associated with increased risk of AAA and identified patients at heightened risk for fast-growing AAA and recommended surgical intervention. TMAO may help identify individuals who may benefit from more frequent surveillance imaging and early surgical intervention to prevent aortic dissection or rupture.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamacardio.2025.2698","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T15:00:37Z","timestamp":1755702037000},"page":"1000","source":"Crossref","is-referenced-by-count":13,"title":["Circulating Trimethylamine <i>N<\/i>-Oxide and Growth Rate of Abdominal Aortic Aneurysms and Surgical Risk"],"prefix":"10.1001","volume":"10","author":[{"given":"Scott J.","family":"Cameron","sequence":"first","affiliation":[{"name":"Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio"},{"name":"Department of Cardiovascular Medicine, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinmin 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