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Dietary Meat, Trimethylamine N-Oxide-Related Metabolites, and Incident Cardiovascular Disease Among Older Adults: The Cardiovascular Health Study.

TitleDietary Meat, Trimethylamine N-Oxide-Related Metabolites, and Incident Cardiovascular Disease Among Older Adults: The Cardiovascular Health Study.
Publication TypeJournal Article
Year of Publication2022
AuthorsWang, M, Wang, Z, Lee, Y, Lai, HTM, Otto, MC de Olive, Lemaitre, RN, Fretts, A, Sotoodehnia, N, Budoff, M, DiDonato, JA, McKnight, B, Tang, WHWilson, Psaty, BM, Siscovick, DS, Hazen, SL, Mozaffarian, D
JournalArterioscler Thromb Vasc Biol
Volume42
Issue9
Paginatione273-e288
Date Published2022 09
ISSN1524-4636
KeywordsAnimals, Atherosclerosis, Cardiovascular Diseases, Carnitine, Humans, Meat, Methylamines, Risk Factors
Abstract<p><b>BACKGROUND: </b>Effects of animal source foods (ASF) on atherosclerotic cardiovascular disease (ASCVD) and underlying mechanisms remain controversial. We investigated prospective associations of different ASF with incident ASCVD and potential mediation by gut microbiota-generated trimethylamine N-oxide, its L-carnitine-derived intermediates γ-butyrobetaine and crotonobetaine, and traditional ASCVD risk pathways.</p><p><b>METHODS: </b>Among 3931 participants from a community-based US cohort aged 65+ years, ASF intakes and trimethylamine N-oxide-related metabolites were measured serially over time. Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, other atherosclerotic death) was adjudicated over 12.5 years median follow-up. Cox proportional hazards models with time-varying exposures and covariates examined ASF-ASCVD associations; and additive hazard models, mediation proportions by different risk pathways.</p><p><b>RESULTS: </b>After multivariable-adjustment, higher intakes of unprocessed red meat, total meat, and total ASF associated with higher ASCVD risk, with hazard ratios (95% CI) per interquintile range of 1.15 (1.01-1.30), 1.22 (1.07-1.39), and 1.18 (1.03-1.34), respectively. Trimethylamine N-oxide-related metabolites together significantly mediated these associations, with mediation proportions (95% CI) of 10.6% (1.0-114.5), 7.8% (1.0-32.7), and 9.2% (2.2-44.5), respectively. Processed meat intake associated with a nonsignificant trend toward higher ASCVD (1.11 [0.98-1.25]); intakes of fish, poultry, and eggs were not significantly associated. Among other risk pathways, blood glucose, insulin, and C-reactive protein, but not blood pressure or blood cholesterol, each significantly mediated the total meat-ASCVD association.</p><p><b>CONCLUSIONS: </b>In this large, community-based cohort, higher meat intake associated with incident ASCVD, partly mediated by microbiota-derived metabolites of L-carnitine, abundant in red meat. These novel findings support biochemical links between dietary meat, gut microbiome pathways, and ASCVD.</p>
DOI10.1161/ATVBAHA.121.316533
Alternate JournalArterioscler Thromb Vasc Biol
PubMed ID35912635
PubMed Central IDPMC9420768
Grant ListU01 HL080295 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
R01 HL103866 / HL / NHLBI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 HL135920 / HL / NHLBI NIH HHS / United States
S10 OD016346 / OD / NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
R01 HL130819 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
75N92021D00006 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
ePub date: 
22/09