Evidence map›Paper›PMID 42455761›Full record

ArticleEuropean heart journal2026

Gut microbe-generated metabolite trimethylamine N-oxide and risk of abdominal aortic aneurysm: a cohort study.

Xinmin S Li, Meng Wang, Zeneng Wang, Bingbing Fan, Melissa Y Tian, Jesse Filippazzo, Yujin Lee, Deepthi P Mallela, Karis Mao, Yang Liu and 14 more

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Article in European heart journal, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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1citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

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1 citing paper in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

24 authors.

Xinmin S LiDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.ORCID 0000-0003-4946-4271
Meng WangFood is Medicine Institute, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.ORCID 0000-0001-8345-9180
Zeneng WangDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.ORCID 0000-0002-6455-8228
Bingbing FanFood is Medicine Institute, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.ORCID 0000-0002-0680-9316
Melissa Y TianDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Jesse FilippazzoDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Yujin LeeDepartment of Food and Nutrition, Myongji University, Yongin, South Korea.ORCID 0000-0002-6948-2525
Deepthi P MallelaDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Karis MaoDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Yang LiuDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Rozenn N LemaitreDepartment of Epidemiology, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7038-1844
Victor XieDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Emilia DiazDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Joseph A DiDonatoDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.ORCID 0000-0002-1641-1758
W H Wilson TangDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.ORCID 0000-0002-8335-735X
Marcia C de Oliveira OttoDeparment of Epidemiology, The University of Texas Health Science Center at Houston School of Public Health, Houston, TX, USA.ORCID 0000-0002-4585-0688
Matthew J BudoffDepartment of Medicine, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.ORCID 0000-0002-9616-1946
A Phillip OwensDepartment of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.ORCID 0000-0002-0835-620X
Anne B NewmanDepartment of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-0106-1150
Scott J CameronDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.ORCID 0000-0002-9616-1540
David S SiscovickDepartment of Research, The New York Academy of Medicine, New York, NY, USA.ORCID 0000-0003-0461-175X
Aldons J LusisDepartment of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.ORCID 0000-0001-9013-0228
Dariush MozaffarianFood is Medicine Institute, Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.ORCID 0000-0001-7958-9492
Stanley L HazenDepartment of Heart, Blood, and Kidney Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.ORCID 0000-0001-7124-6639

Funding

Project 3: Microbiota generated aryl sulfates and secondary bile acids in cardiometabolic diseaseP01HL147823 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MICHAEL ANDREW FISCHBACH · 2019 to 2026
$17.0M
Gut Flora Metabolism of Dietary Phosphatidylcholine and CVDR01HL103866 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI HAZEN, STANLEY L · 2010 to 2023
$10.8M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
TMAO and Initiation, Extent, and Clinical Onset of Atherosclerotic CVDR01HL135920 · NHLBI · TUFTS UNIVERSITY BOSTON · PI Stanley L Hazen, DARIUSH MOZAFFARIAN · 2017 to 2026
$8.7M
CARDIOVASCULAR HEALTH STUDY (CHS) - TASK AREA C, STUDY CLOSEOUT75N92021D00006 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE · 2021 to 2024
$8.4M
CHS research resources for the cardiovascular health of older adultsU01HL130114 · NHLBI · UNIVERSITY OF WASHINGTON · PI BURKE, GREGORY L, KRONMAL, RICHARD A · 2016 to 2019
$6.6M
CHS Events Follow-up StudyU01HL080295 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2005 to 2008
$4.6M
Infrastructure for mentored access to CHS data and specimensR01HL172803 · NHLBI · UNIVERSITY OF WASHINGTON · PI James S Floyd, Michelle Christina Odden · 2025 to 2026
$2.7M
Role of the Gut Microbiota in Abdominal Aortic AneurysmR01HL147171 · NHLBI · UNIVERSITY OF CINCINNATI · PI OWENS III, ALBERT PHILLIP · 2020 to 2023
$2.5M
Platelets as Biosensors and Mediators of Aortic Aneurysm GrowthR01HL158801 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI CAMERON, SCOTT JAMES · 2021 to 2025
$2.5M
Gut microbial dietary phenylalanine metabolism and heart failureR01HL167831 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI Stanley L Hazen · 2024 to 2026
$2.4M
CHSNHLBI NIH HHS 75N92021D00006NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01HC55222NHLBI NIH HHS N01HC85079NHLBI NIH HHS N01HC85080NHLBI NIH HHS N01HC85081NHLBI NIH HHS N01HC85082NHLBI NIH HHS N01HC85083NHLBI NIH HHS N01HC85086NHLBI NIH HHS P01 HL147823NHLBI NIH HHS R01 HL103866NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL135920NHLBI NIH HHS R01 HL147171NHLBI NIH HHS R01-HL147171NHLBI NIH HHS R01 HL158801NHLBI NIH HHS R01HL158801NHLBI NIH HHS R01 HL167831NHLBI NIH HHS R01 HL172803NHLBI NIH HHS R01HL172803NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01HL080295NHLBI NIH HHS U01 HL130114NHLBI NIH HHS U01HL130114NIA NIH HHS R01 AG023629NIH HHSNINDS NIH HHS R01AG023629Office of Dietary Supplements
6 · The paper itself

Abstract

BACKGROUND AND

aimsAbdominal aortic aneurysms (AAAs) are associated with increased mortality in older adults. The gut microbe-generated metabolite trimethylamine N-oxide (TMAO) has been linked to AAA risk and promotes AAA progression in animal models. Whether circulating TMAO levels in apparently healthy older adults predict AAA development and adverse AAA outcomes remains unknown.

methodsPlasma TMAO levels were quantified using stable isotope dilution liquid chromatography-tandem mass spectrometry in 4442 community-dwelling adults (aged ≥65 years) in the Cardiovascular Health Study. Participants underwent ultrasound screening and prospective follow-up. Multivariable models assessed associations of serial TMAO levels with AAA development and incident risk for adverse AAA events, adjusting for traditional risk factors, renal function, socioeconomic status, and cardiometabolic lifestyle factors.

resultsHigher baseline TMAO levels were associated with larger infrarenal aortic diameter and increased AAA risk. Over a median 12.2-year follow-up (54 402 person-years), 79 participants experienced incident adverse AAA events (repair, rupture, or AAA-related death). Elevated TMAO levels were independently associated with higher risk of adverse AAA events, whether modelled continuously [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.07-1.54 per doubling], by quantiles (HR for tertile 3 vs tertile 1: 2.46, 95% CI 1.32-4.59), or using a clinical threshold (≥6.2 µM; HR 1.93, 95% CI 1.25-2.99).

conclusionsIn community-based older adults, higher TMAO levels were independently associated with increased risk of AAA development and adverse AAA events. Findings support TMAO as a novel risk factor for AAA and a potential therapeutic target for AAA prevention.

Indexed as

AAA repairAbdominal aortic aneurysmsAneurysm ruptureGut microbiomeTMAO

Identifiers

PMID42455761
PMCPMC13630272

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