Po-02-162 the relationship of dietary trimethylamines with incident atrial fibrillation in a large longitudinal cohort

Despite the advent of catheter ablation and antiarrhythmic medications, atrial fibrillation (AF) remains a significant source or morbidity and mortality. The gut microbiome and microbial derived trimethylamine N-oxide (TMAO) have been increasingly recognized as having a novel role in cardiovascular disease. To examine the relationship of TMAO and related dietary trimethylamines with incident AF in a combined analysis of two large, community-based, prospective cohorts with cardiovascular outcomes. We examined 11,751 individuals from two community-based cohorts, the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis, followed prospectively for incident AF. Plasma concentrations of dietary trimethylamines (TMAO, choline, betaine, carnitine, and γ-butyrobetaine crotonobetaine (crotono)) were measured by high-performance liquid chromatography and tandem mass spectrometry at baseline and, in some subjects, at a follow-up visit. AF was ascertained using diagnosis codes assigned at hospital discharge and in outpatient care. Time-varying multivariable Cox proportional hazard models were used to assess associations of plasma concentrations of dietary trimethylamines with incident AF after adjustment for age, sex race, visit site, BMI, waist circumference, HDL, LDL, smoking, SBP, treated HTN, PR-interval, prevalent MI, CHF, diabetes, and stroke. During a median follow-up of 13.6 years, 3069 incident atrial fibrillation events were identified. Higher plasma TMAO, choline, betaine, and crotono concentrations were each associated with greater AF risk; adjusted hazard ratios per one standard deviation higher TMAO: 1.07 [95% CI, 1.03-1.11, P<0.01]; choline 1.25 [95% CI, 1.11-1.39, P<0.01]; betaine 1.16 [95% CI, 1.07-1.26, P<0.01]; and crotono 1.15 [95% CI, 1.09-1.22, P<0.01]). In exploratory analyses, the risk of AF associated with TMAO and crotono was higher for participants with greater BMI (P-value for interaction 0.004 and 0.003, respectively) (Figure1). TMAO and related dietary trimethylamines were independently associated with incident AF, and in exploratory analyses the gut microbial products TMAO and crotono confer increasing AF risk with obesity. These data may provide preliminary evidence for an association between dietary trimethylamines, the gut microbiome, obesity, and AF.