Microbiota-dependent metabolite trimethylamine n-oxide and coronary artery calcium in the coronary artery risk development in young adults study (CARDIA)

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. © 2016 the authors.