Author + information
- Received November 7, 2019
- Accepted November 27, 2019
- Published online February 17, 2020.
- Yoriko Heianza, RD, PhDa,
- Wenjie Ma, MD, PhDb,
- Joseph A. DiDonato, PhDc,
- Qi Sun, MD, ScDd,e,
- Eric B. Rimm, ScDd,e,f,
- Frank B. Hu, MD, PhDd,e,f,
- Kathryn M. Rexrode, MD, MPHe,g,h,
- JoAnn E. Manson, MD, DrPhe,f,g and
- Lu Qi, MD, PhDa,d,e,∗ (, )@TulaneSPHTM
- aDepartment of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, Louisiana
- bClinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts
- cDepartment of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, Ohio
- dDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- eChanning Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- fDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- gDivision of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- hDivision of Women’s Health, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Lu Qi, Department of Nutrition, Harvard T.H. Chan School of Public Health, Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal Street, Suite 1724, New Orleans, Louisiana 70112.
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.
The study is supported by National Institutes of Health grants from the National Cancer Institute (UM1 CA186107 and CA49449), the National Heart, Lung, and Blood Institute (R01 HL034594, R01 HL088521, HL071981, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718, DK100383, DK078616, DK115679), a National Institutes of Health–shared instrumentation grant (S10OD016346), the Boston Obesity Nutrition Research Center (DK46200), and United States–Israel Binational Science Foundation Grant 2011036. The sponsors had no role in the design or conduct of the study. Dr. Heianza was a recipient of a Grant-in-Aid for Scientific Research, a Postdoctoral Fellowship for Research Abroad from the Japan Society for the Promotion of Science, and the 2019 AHA postdoctoral fellowship award (19POST34380035). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received November 7, 2019.
- Accepted November 27, 2019.
- 2020 American College of Cardiology Foundation
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