John Jeffrey Carr
Professor of Radiology, Biomedical Informatics and Cardiovascular Medicine
Last active: 1/10/2020

Microbiota-Dependent Metabolite Trimethylamine N-Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA).

Meyer KA, Benton TZ, Bennett BJ, Jacobs DR, Lloyd-Jones DM, Gross MD, Carr JJ, Gordon-Larsen P, Zeisel SH
J Am Heart Assoc. 2016 5 (10)

PMID: 27792658 · PMCID: PMC5121500 · DOI:10.1161/JAHA.116.003970

BACKGROUND - Clinical studies implicate trimethylamine N-oxide (TMAO; a gut microbiota-dependent nutrient metabolite) in cardiovascular disease risk. There is a lack of population-based data on the role of TMAO in advancing early atherosclerotic disease. We tested the prospective associations between TMAO and coronary artery calcium (CAC) and carotid intima-media thickness (cIMT).

METHODS AND RESULTS - Data were from the Coronary Artery Risk Development in Young Adults Study (CARDIA), a biracial cohort of US adults recruited in 1985-1986 (n=5115). We randomly sampled 817 participants (aged 33-55 years) who attended examinations in 2000-2001, 2005-2006, and 2010-2011, at which CAC was measured by computed tomography and cIMT (2005-2006) by ultrasound. TMAO was quantified using liquid chromotography mass spectrometry on plasma collected in 2000-2001. Outcomes were incident CAC, defined as Agatston units=0 in 2000-2001 and >0 over 10-year follow-up, CAC progression (any increase over 10-year follow-up), and continuous cIMT. Over the study period, 25% (n=184) of those free of CAC in 2000-2001 (n=746) developed detectable CAC. In 2000-2001, median (interquartile range) TMAO was 2.6 (1.8-4.2) μmol/L. In multivariable-adjusted models, TMAO was not associated with 10-year CAC incidence (rate ratio=1.03; 95% CI: 0.71-1.52) or CAC progression (0.97; 0.68-1.38) in Poisson regression, or cIMT (beta coefficient: -0.009; -0.03 to 0.01) in linear regression, comparing the fourth to the first quartiles of TMAO.

CONCLUSIONS - In this population-based study, TMAO was not associated with measures of atherosclerosis: CAC incidence, CAC progression, or cIMT. These data indicate that TMAO may not contribute significantly to advancing early atherosclerotic disease risk among healthy early-middle-aged adults.

© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

MeSH Terms (19)

Adult African Americans Atherosclerosis Carotid Intima-Media Thickness Coronary Artery Disease Disease Progression European Continental Ancestry Group Female Gastrointestinal Microbiome Humans Incidence Longitudinal Studies Male Methylamines Middle Aged Prospective Studies Tomography, X-Ray Computed United States Vascular Calcification

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