AIMS: Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients. METHODS AND RESULTS: We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4-6.2)μM, 9.8 (7.9-12.2)μM, and 41.1 (32.5-52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r = 0.33, P < 0.001) and less between TMAO and betaine (r = 0.09, P < 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P < 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.03-1.74), P < 0.05], and betaine levels [1.33 (1.03-1.73), P < 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated. CONCLUSION: Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO.
AIMS: Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients. METHODS AND RESULTS: We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4-6.2)μM, 9.8 (7.9-12.2)μM, and 41.1 (32.5-52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r = 0.33, P < 0.001) and less between TMAO and betaine (r = 0.09, P < 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P < 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.03-1.74), P < 0.05], and betaine levels [1.33 (1.03-1.73), P < 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated. CONCLUSION: Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO.
Entities:
Keywords:
Cardiovascular disease; Choline; Gut microbiota; Myocardial infarction; Nutrition
Authors: Rebecca M LeLeiko; Christopher S Vaccari; Srikanth Sola; Nadya Merchant; Sameer H Nagamia; Martin Thoenes; Bobby V Khan Journal: Am J Cardiol Date: 2009-06-24 Impact factor: 2.778
Authors: Richard Body; Caroline A Griffith; Brian Keevil; Garry McDowell; Simon Carley; Jamie Ferguson; Kevin Mackway-Jones Journal: Clin Chim Acta Date: 2009-03-31 Impact factor: 3.786
Authors: Zeneng Wang; Elizabeth Klipfell; Brian J Bennett; Robert Koeth; Bruce S Levison; Brandon Dugar; Ariel E Feldstein; Earl B Britt; Xiaoming Fu; Yoon-Mi Chung; Yuping Wu; Phil Schauer; Jonathan D Smith; Hooman Allayee; W H Wilson Tang; Joseph A DiDonato; Aldons J Lusis; Stanley L Hazen Journal: Nature Date: 2011-04-07 Impact factor: 49.962
Authors: Aurelian Bidulescu; Lloyd E Chambless; Anna Maria Siega-Riz; Steven H Zeisel; Gerardo Heiss Journal: Nutr J Date: 2009-02-20 Impact factor: 3.271
Authors: Zeneng Wang; Adam B Roberts; Jennifer A Buffa; Bruce S Levison; Weifei Zhu; Elin Org; Xiaodong Gu; Ying Huang; Maryam Zamanian-Daryoush; Miranda K Culley; Anthony J DiDonato; Xiaoming Fu; Jennie E Hazen; Daniel Krajcik; Joseph A DiDonato; Aldons J Lusis; Stanley L Hazen Journal: Cell Date: 2015-12-17 Impact factor: 41.582
Authors: Kathryn M Camp; Danuta Krotoski; Melissa A Parisi; Katrina A Gwinn; Bruce H Cohen; Christine S Cox; Gregory M Enns; Marni J Falk; Amy C Goldstein; Rashmi Gopal-Srivastava; Gráinne S Gorman; Stephen P Hersh; Michio Hirano; Freddie Ann Hoffman; Amel Karaa; Erin L MacLeod; Robert McFarland; Charles Mohan; Andrew E Mulberg; Joanne C Odenkirchen; Sumit Parikh; Patricia J Rutherford; Shawne K Suggs-Anderson; W H Wilson Tang; Jerry Vockley; Lynne A Wolfe; Steven Yannicelli; Philip E Yeske; Paul M Coates Journal: Mol Genet Metab Date: 2016-09-20 Impact factor: 4.797
Authors: Carlee I Oakley; Julian A Vallejo; Derek Wang; Mark A Gray; LeAnn M Tiede-Lewis; Tilitha Shawgo; Emmanuel Daon; George Zorn; Jason R Stubbs; Michael J Wacker Journal: Am J Physiol Heart Circ Physiol Date: 2020-04-03 Impact factor: 4.733