Lee Y, Nemet I, Wang Z, et al. - Higher risk of incident atherosclerotic cardiovascular disease (ASCVD: myocardial infarction, fatal coronary heart disease, stroke, sudden cardiac death, or other atherosclerotic death) was observed in relation to serial measures of trimethylamine N‐oxide (TMAO) in a large community‐based cohort of older US adults, and this relationship was apparently modified by presence of impaired renal function and with higher risk of recurrent ASCVD.

• This study involved 4131 (incident) and 1449 (recurrent) older US adults.

• To determine TMAO, stable isotope dilution liquid chromatography–tandem mass spectrometry was employed at baseline and 7 years.

• TMAO is a gut microbiota‐dependent metabolite of dietary choline, L‐carnitine, and phosphatidylcholine‐rich foods.

• Prospective follow‐up revealed occurrences of 1766 incident and 897 recurrent ASCVD events.

• Higher risk of incident ASCVD was noted in relation to higher levels of TMAO, post- multivariable adjustment, with extreme quintile hazard ratio vs the lowest quintile = 1.21.

• In cases with impaired renal function, high levels of TMAO were related to higher incidence of ASCVD; this was not seen in the presence of normal or mildly reduced renal function.

• Participants with prior ASCVD showed a link of TMAO with higher risk of recurrent ASCVD, without significant modification by estimated glomerular filtration rate.