title: Microbiota-Dependent Metabolite Trimethylamine N-Oxide and Coronary Artery Calcium in the Coronary Artery Risk Development in Young Adults Study (CARDIA).
abstract: 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).
  
  
  
  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.
  
  
  
  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.
authors: Department of Nutrition, Gillings School of Global Public Health & School of Medicine, University of North Carolina, Chapel Hill, NC ktmeyer@unc.edu.
authors: Katie A
authors: KA
authors: Meyer
authors: Nutrition Research Institute, University of North Carolina, Chapel Hill, NC.
authors: Thomas Z
authors: TZ
authors: Benton
authors: Department of Nutrition, Gillings School of Global Public Health & School of Medicine, University of North Carolina, Chapel Hill, NC Nutrition Research Institute, University of North Carolina, Chapel Hill, NC Department of Genetics, University of North Carolina, Chapel Hill, NC.
authors: Brian J
authors: BJ
authors: Bennett
authors: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN.
authors: David R
authors: DR
authors: Jacobs
authors: Department of Preventive Medicine, Northwestern University, Chicago, IL.
authors: Donald M
authors: DM
authors: Lloyd-Jones
authors: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN.
authors: Myron D
authors: MD
authors: Gross
authors: Department of Radiology and Radiological Sciences and Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN.
authors: J Jeffrey
authors: JJ
authors: Carr
authors: Department of Nutrition, Gillings School of Global Public Health & School of Medicine, University of North Carolina, Chapel Hill, NC Carolina Population Center, University of North Carolina, Chapel Hill, NC.
authors: Penny
authors: P
authors: Gordon-Larsen
authors: Department of Nutrition, Gillings School of Global Public Health & School of Medicine, University of North Carolina, Chapel Hill, NC Nutrition Research Institute, University of North Carolina, Chapel Hill, NC.
authors: Steven H
authors: SH
authors: Zeisel
mesh_terms: D000328:Adult; D001741:Black or African American; D050197:Atherosclerosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D059168:Carotid Intima-Media Thickness; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology; D061205:Vascular Calcification / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D044465:White People
chemical_list: D008744:Methylamines; C005855:trimethyloxamine
keywords: atherosclerosis; biomarker; epidemiology; follow‐up study; risk factor