期刊
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
卷 75, 期 7, 页码 763-772出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2019.11.060
关键词
coronary heart disease; diet; gut-microbial metabolites; prospective cohort study; risk factors
资金
- National Institutes of Health grants from the National Cancer Institute [UM1 CA186107, CA49449]
- National Heart, Lung, and Blood Institute [R01 HL034594, R01 HL088521, HL071981, HL126024]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK091718, DK100383, DK078616, DK115679]
- National Institutes of Health-shared instrumentation grant [S10OD016346]
- Boston Obesity Nutrition Research Center [DK46200]
- United States-Israel Binational Science Foundation [2011036]
- Japan Society for the Promotion of Science
- 2019 AHA postdoctoral fellowship award [19POST34380035]
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 (D) in TMAO were calculated. Incident cases of CHD (n 1/4 380) were identified after the second blood collection through 2016 and were matched to controls (n 1/4 380). 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 DTMAO-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 DTMAO with CHD risk. (c) 2020 by the American College of Cardiology Foundation.
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