Serum gut microbe-dependent trimethylamine N-oxide improves the prediction of future cardiovascular disease in a community-based general population

Background and aims: Recent studies have shown that trimethylamine N-oxide (TMAO) is a risk factor for cardiovascular disease (CVD) in different clinical settings, but few studies confirmed the association in a community- based general population. Methods: This is a nested case-control study from a prospective cohort design. A total of 86 newly diagnosed CVD cases with a median follow-up period of 4.83 years and 86 matched controls were selected for the present analysis. Results: Using the LC-MS/MS assays, we found that new CVD cases had a higher baseline levels of TMAO than controls [ median (inter-quartile): 1.57 (0.79-2.29) mu mol/L v. s 0.68 (0.23-1.40) mu mol/L, p < 0.001]. After multivariable adjustment, individuals with TMAO >= 1.89 mu mol/L (Q4) and 1.05-1.89 mu mol/L (Q3) had odds ratio (OR) for CVD of 2.735 [ 95% confidence interval (CI): 1.328-5.630] and 2.544 (95% CI: 1.251-5.172) with the lowest quartile (< 0.43 mu mol/L) as reference. In addition, comparisons of areas under receiver operator characteristics curves confirmed that a model including TMAO had a better discrimination than one without (0.732 vs. 0.664, p = 0.045). Conclusions: In the community-based general population, there was a positive association between TMAO and future risk of CVD. Addition of TMAO improved the prediction of CVD beyond traditional risk factors. We recommend considering TMAO as a potential novel preventive target in the management of low-risk CVD adults.