Abstract MP053: Dietary Trimethylamine Intake and Cardiovascular Mortality Among Urban Chinese Adults

Abstract

Background: Trimethylamine (TMA)-containing nutrients (choline, betaine and carnitine) are dietary precursors of a gut microbial-derived metabolite, trimethylamine-N-oxide (TMAO). Studies have suggested that elevated TMAO contributes to atherosclerosis and increased mortality in cardiovascular disease (CVD) patients. However, epidemiological evidence remains limited regarding whether high TMA intake may increase CVD mortality. No population-based study has evaluated animal vs. plant food-derived TMA in relation to CVD. Objective: We examined dietary TMA, from animal-source foods (e.g., eggs, red meat and fish) and/or from plant foods (e.g., soy foods, legumes and vegetables), in association with total CVD mortality and mortality from coronary heart disease (CHD) and ischemic and hemorrhagic stroke. We also evaluated whether the associations were modified by food sources of TMA and by major CVD risk factors. Methods: Included were 73216 women and 61190 men from two prospective cohort studies of Chinese adults. They were 40-74 years of age, free of cancer and with a plausible energy intake at baseline. Usual diets were assessed using food-frequency questionnaires. Dietary TMA intake was calculated using the USDA database. Vital status and cause of death were obtained via linkages with the vital statistics registry. Cox model was used to estimate HRs and 95% CIs. Results: During a mean follow-up of 12.5 years, we documented 3740 CVD deaths. After adjusting for potential confounders, including sociodemographics, lifestyle, disease history, and other dietary risk factors, high TMA intake was associated with increased mortality from total CVD and CHD–HR (95% CI) in the highest vs. lowest quintile of TMA intake was 1.33 (1.15, 1.53) for CVD mortality and 1.60 (1.25, 2.06) for CHD mortality; both p-trend=0.0001. A positive trend of association was also observed for ischemic stroke mortality (HR [95% CI] =1.31 [0.99, 1.74]), but not for hemorrhagic stroke mortality. With mutual adjustment, animal- and plant-sourced TMA showed similar magnitude of positive associations with CVD and CHD mortality–HR (95% CI) in the highest vs. lowest quintile was 1.13 (0.99, 1.29) for animal-TMA and 1.19 (1.07, 1.33) for plant-TMA related to CVD mortality, and 1.33 (1.05, 1.67) for animal-TMA and 1.29 (1.07, 1.57) for plant-TMA related to CHD mortality. The TMA-CVD mortality association seemed more evident in men than in women and among adults with higher socioeconomic status, higher waist-hip ratios, higher refined carbohydrate intakes, or diabetes, although no interactions were statistically significant. Conclusion: Our study suggests that high TMA intake, from either animal or plant food sources, is associated with increased mortality from atherosclerotic CVD among urban Chinese adults. Potential mechanism involving gut microbial production of TMAO needs to be investigated in future studies.