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) lmol/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.
Bibliographical noteFunding Information:
This work was supported by grants from the National Heart, Lung and Blood Institute (NHLBI) for statistical analysis and manuscript preparation (K01-HL127159; Meyer) and for measurement and analysis of CAC (R01-HL098445; Carr); Egg Nutrition Center (Meyer) and UNC Nutrition Research Institute (Meyer) for TMAO assays; and National Institute of Diabetes and Digestive and Kidney Diseases (P30-DK056350; Zeisel) for general support. The Coronary Artery Risk Development in Young Adults Study (CARDIA) is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268201300028C, HHSN268 201300029C, and HHSN268200900041C from the NHLBI, the Intramural Research Program of the National Institute on Aging (NIA), and an intra-agency agreement between the NIA and NHLBI (AG0005).
© 2016 The Authors.
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