American College of Cardiology Foundation

02/18/2020 | Press release | Distributed by Public on 02/18/2020 16:36

Gut Microbial Metabolite Trimethylamine N-Oxide Changes and CHD Risk

Study Questions:

Are 10-year changes in plasma trimethylamine N-oxide (TMAO) levels associated with coronary heart disease (defined as nonfatal myocardial infarction [MI] and fatal coronary heart disease [CHD]) incidence?


A prospective nested case-control study was conducted in 760 healthy women participating in the Nurses' Health Study. Plasma TMAO levels were measured both at the first (1989-1990) and the second (2000-2002) blood collections; 10-year changes in TMAO (ΔTMAO) were calculated. Incident cases of CHD (n = 380) were identified after the second blood collection through 2016 and were matched to controls (n = 380).


Regardless of the initial TMAO levels, 10-year increases in TMAO from the first to second blood collection were significantly associated with an increased risk of CHD (relative risk [RR] in the top tertile, 1.58; RR per 1-standard deviation increment, 1.33). Participants with elevated TMAO levels at both time points showed the highest RR of 1.79 for CHD as compared with those with consistently low TMAO levels. The ΔTMAO-CHD relationship was strengthened by unhealthy dietary patterns (assessed by the Alternate Healthy Eating Index [AHEI]) and was attenuated by healthy dietary patterns (p interaction = 0.008).


Long-term increases in TMAO are associated with higher CHD risk, and repeated assessment of TMAO over 10 years improves the identification of people with a higher risk of CHD. Diet may modify the associations of ΔTMAO with CHD risk.


The intestinal microbiota metabolizes choline and L-carnitine (which are abundant in animal protein) to TMAO, the serum level of which has been shown to be a marker of atherosclerotic cardiovascular disease burden in some studies, including carotid plaque burden and coronary plaque vulnerability. It is thought to help explain the increase in cardiovascular risk associated with meat and particularly processed meat products such as bacon. This is the first study to demonstrate a relationship between changes in TMAO and CHD risk. The AHEI used in the study was designed to assess adherence to US dietary guidelines. Men and women with AHEI scores in the top versus bottom quintile had a significant 20% and 11% reduction in overall major chronic disease, respectively. Reductions were stronger for cardiovascular disease risk in both men (RR, 0.61) and women (RR, 0.72).

Clinical Topics:Diabetes and Cardiometabolic Disease, Prevention, Diet

Keywords:Atherosclerosis, Carnitine, Choline, Chronic Disease, Coronary Disease, Diet, Meat Products, Metabolic Syndrome X, Methylamines, Myocardial Infarction, Nutrition Policy, Oxides, Primary Prevention, Risk Factors

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