Objective: Trimethylamine N-oxide (TMAO), a gut microbiota-dependent nutrient metabolite, has been implicated in the development of cardiovascular disease (CVD). TMAO is excreted in the urine and high levels may reflect poor kidney function, an independent risk factor for CVD. We tested the association between TMAO and coronary artery calcium (CAC) in a young, healthy sample of US adults with normal kidney function.
Methods: Study participants were from the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a multicenter cohort of black and white Americans established in 1985/86 (baseline n=5,115; ages 18-30). CAC was measured at follow-up years 15, 20, and 25 with computed tomography (CT). Among a subsample of participants with no detectable CAC at year 15 who had complete CAC data (years 15, 20, 25) and covariate data (year 15) (n=746), we measured TMAO (uM) in year 15 stored plasma (-70 C) and defined incident CAC as having total Agatston units ≥ 0 across all arteries at year 20 or 25. TMAO was measured by using liquid chromatography mass spectrometry. Multivariable-adjusted logistic regression was used to estimate the 10-year incidence of CAC (% who developed any CAC) across quartiles of year 15 TMAO.
Results: Among 746 participants without CAC at year 15, 184 developed CAC over the 10-year study period. TMAO was not associated with incident CAC in multivariable-adjusted logistic regression models, controlling for demographic, behavioral, and biologic covariates (see Table). Comparing quintiles 1 and 5 of TMAO, the multivariable-adjusted risk (%) of the cohort who developed CAC over the 10-year period was 26% (95% CI: 18%-36%) and 22% (16%-31%), respectively.
Conclusion: In this population-based cohort of healthy middle-aged US adults with normal kidney function (99% eGFR≥60 ml/min/1.73 m2), TMAO was not associated with incident CAC over 10 years of follow-up. These findings do not support a role for TMAO in the progression of atherosclerosis among young (33-45 y) healthy individuals with normal kidney function.