TY - JOUR
T1 - Plasma trimethylamine N-oxide (TMAO) levels predict future risk of coronary artery disease in apparently healthy individuals in the EPIC-Norfolk prospective population study
AU - Tang, W. H. Wilson
AU - Li, Xinmin S.
AU - Wu, Yuping
AU - Wang, Zeneng
AU - Khaw, Kay-Tee
AU - Wareham, Nicholas J.
AU - Nieuwdorp, Max
AU - Boekholdt, S. Matthijs
AU - Hazen, Stanley L.
N1 - Funding Information:
The EPIC-Norfolk Study is funded by Cancer Research UK grant number 14136 and the Medical Research Council grant number G1000143 . This research was supported by grants from the National Institutes of Health (NIH) and the Office of Dietary Supplements ( R01HL103866, R01DK106000, R01HL126827, WT and SH ; P01HL-147823 to SH, R01HL130819 to ZW ). MN is supported by a personal ZONMW-VIDI grant 2013 [016.146.327] and a Dutch Heart Foundation CVON IN CONTROL Young Talent Grant 2013 . Dr. Hazen was partially supported by a gift from the Leonard Krieger endowment. Mass spectrometry studies were performed on instruments housed in a facility supported in part by the Case Western Reserve University CTSA ( UL1TR000439 ), and a Center of Innovations Award by Shimadzu. The study reported here was additionally supported by Le Ducq consortium grant 17CVD01 (to MN and SH)
Publisher Copyright:
© 2021 Elsevier Inc.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - Background: Recent studies show a mechanistic link between gut microbiota-dependent formation of the atherosclerosis- and thrombosis-promoting metabolite trimethylamine N-oxide (TMAO) and cardiovascular disease (CVD). The clinical utility of TMAO in apparently healthy subjects for predicting incident CVD risks is unclear. Methods and Results: In the EPIC-Norfolk community-based study, we examined baseline fasting levels of TMAO and two of its nutrient precursors, choline and betaine, in a case:control design study comparing apparently European healthy middle-aged participants who subsequently develop CVD (Cases, n = 908) vs those who did not (Controls, n = 1,273) over an ensuing average follow-up period of 8 years. In participants who developed CVD vs controls, higher plasma TMAO (3.70 [IQR 2.50-6.41]μM vs 3.25 [IQR 2.19-52,1.15]μM; P <.001) and choline levels (9.09 [IQR 7.87-10.53]μM vs 8.89 [IQR 7.66-10.13]μM; P =.001) were observed. Following adjustments for traditional risk factors, elevated TMAO (adjusted odds ratio (OR) 1.58 [95% confidence interval (CI) 1.21-2.06], P <.001) and choline levels (adjusted OR 1.31 [95%CI 1.00-1.72], P <.05) remained predictive of incident CVD development. The clinical prognostic utility of TMAO remained significant and essentially unchanged regardless of the level of cutoff chosen between 1.5 uM (10%ile) to 10.5 uM (90%ile). Conclusion: In apparently healthy participants of the community-based middle-aged EPIC-Norfolk population, elevated plasma levels of the gut microbe-dependent metabolite TMAO, and its nutrient precursor choline, predict incident risk for CVD development independent of traditional risk factors.
AB - Background: Recent studies show a mechanistic link between gut microbiota-dependent formation of the atherosclerosis- and thrombosis-promoting metabolite trimethylamine N-oxide (TMAO) and cardiovascular disease (CVD). The clinical utility of TMAO in apparently healthy subjects for predicting incident CVD risks is unclear. Methods and Results: In the EPIC-Norfolk community-based study, we examined baseline fasting levels of TMAO and two of its nutrient precursors, choline and betaine, in a case:control design study comparing apparently European healthy middle-aged participants who subsequently develop CVD (Cases, n = 908) vs those who did not (Controls, n = 1,273) over an ensuing average follow-up period of 8 years. In participants who developed CVD vs controls, higher plasma TMAO (3.70 [IQR 2.50-6.41]μM vs 3.25 [IQR 2.19-52,1.15]μM; P <.001) and choline levels (9.09 [IQR 7.87-10.53]μM vs 8.89 [IQR 7.66-10.13]μM; P =.001) were observed. Following adjustments for traditional risk factors, elevated TMAO (adjusted odds ratio (OR) 1.58 [95% confidence interval (CI) 1.21-2.06], P <.001) and choline levels (adjusted OR 1.31 [95%CI 1.00-1.72], P <.05) remained predictive of incident CVD development. The clinical prognostic utility of TMAO remained significant and essentially unchanged regardless of the level of cutoff chosen between 1.5 uM (10%ile) to 10.5 uM (90%ile). Conclusion: In apparently healthy participants of the community-based middle-aged EPIC-Norfolk population, elevated plasma levels of the gut microbe-dependent metabolite TMAO, and its nutrient precursor choline, predict incident risk for CVD development independent of traditional risk factors.
UR - http://www.scopus.com/inward/record.url?scp=85103050154&partnerID=8YFLogxK
U2 - 10.1016/j.ahj.2021.01.020
DO - 10.1016/j.ahj.2021.01.020
M3 - Article
C2 - 33626384
VL - 236
SP - 80
EP - 86
JO - American Heart Journal
JF - American Heart Journal
SN - 1097-6744
ER -