Long-Term Changes in Gut Microbial Metabolite Trimethylamine N-Oxide and Coronary Heart Disease Risk.

Abstract

BACKGROUND:

A gut-microbial metabolite, trimethylamine N-oxide (TMAO), has been associated with coronary atherosclerotic burden. No previous prospective study has addressed associations of long-term changes in TMAO with coronary heart disease (CHD) incidence.

OBJECTIVES:

The purpose of this study was to investigate whether 10-year changes in plasma TMAO levels were significantly associated with CHD incidence.

METHODS:

This prospective nested case-control study included 760 healthy women at baseline. Plasma TMAO levels were measured both at the first (1989 to 1990) and the second (2000 to 2002) blood collections; 10-year changes (Δ) in TMAO were calculated. Incident cases of CHD (n = 380) were identified after the second blood collection through 2016 and were matched to controls (n = 380).

RESULTS:

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 [95% confidence interval (CI): 1.05 to 2.38]; RR per 1-SD increment: 1.33 [95% CI: 1.06 to 1.67]). Participants with elevated TMAO levels (the top tertile) at both time points showed the highest RR of 1.79 (95% CI: 1.08 to 2.96) for CHD as compared with those with consistently low TMAO levels. Further, we found that the ΔTMAO-CHD relationship was strengthened by unhealthy dietary patterns (assessed by the Alternate Healthy Eating Index) and was attenuated by healthy dietary patterns (p interaction = 0.008).

CONCLUSIONS:

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

• Authors: Yoriko Heianza, Wenjie Ma, Joseph A DiDonato, Qi Sun, Eric B Rimm, Frank B Hu, Kathryn M Rexrode, JoAnn E Manson, Lu Qi
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 75 Issue 7 Pg. 763-772 (02 25 2020) ISSN: 1558-3597 [Electronic] United States
• PMID: 32081286 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Methylamines
• trimethyloxamine

Topics

• Adult
• Case-Control Studies
• Coronary Disease (blood, epidemiology, microbiology)
• Diet, Healthy
• Female
• Gastrointestinal Microbiome
• Humans
• Incidence
• Massachusetts (epidemiology)
• Methylamines (blood)
• Middle Aged
• Prospective Studies