Associations Among Serum Trimethylamine-N-oxide (TMAO) Levels, Kidney Function and Infarcted Coronary Artery Number in Patients Undergoing Cardiovascular Surgery: a Cross-sectional Study

Overview

Journal Clin Exp Nephrol

Publisher Springer

Specialty Nephrology

Date 2015 Dec 18

PMID 26676906

Citations 43

Authors

Aki Mafune

Takeo Iwamoto

Yusuke Tsutsumi

Akio Nakashima

Izumi Yamamoto

Keitaro Yokoyama

Takashi Yokoo

Mitsuyoshi Urashima

Affiliations

Soon will be listed here.

Abstract

Background: Trimethylamine-N-oxide (TMAO) is a metabolite of phosphatidylcholine generated by gut microbiota and liver enzymes, and has recently been recognized as contributing to atherosclerosis. Elevated serum TMAO levels have been shown to increase the risk of cardiovascular disease (sudden death, myocardial infarction, or stroke) in patients undergoing elective coronary angiography. We aimed to clarify whether TMAO levels are associated with the number of infarcted coronary arteries as a measure of the severity of atherosclerosis, with adjustment using a priori-defined covariates such as kidney function.

Methods: By conducting a cross-sectional study of 227 patients who underwent cardiovascular surgery for coronary artery disease, valvular heart disease, or aortic disease, the association between serum TMAO levels as measured by HPLC-APCI-MS/MS and the number of infarcted coronary arteries was evaluated using ordered logistic regression models with adjustment of 10 covariates, including chronic kidney disease (CKD) stage. Unadjusted and adjusted odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were determined.

Results: Significantly higher TMAO levels were observed in advanced-stage CKD (p ≤ 0.001). In fully adjusted models with the 10 covariates, a significantly increased number of infarcted coronary arteries was identified in the highest quartile and quintile of TMAO compared to the lowest quartile (OR 11.9; 95 % CI 3.88-36.7, p ≤ 0.001) and quintile (OR 14.1; 95 % CI 3.88-51.2; p ≤ 0.001), respectively, independent of dyslipidemia.

Conclusions: Higher serum TMAO levels may be associated with advanced CKD stages and with an increased number of infarcted coronary arteries in patients who undergo cardiovascular surgery.

Citing Articles

Role of Gut Microbial Metabolites in Ischemic and Non-Ischemic Heart Failure.

Hatamnejad M, Medzikovic L, Dehghanitafti A, Rahman B, Vadgama A, Eghbali M Int J Mol Sci. 2025; 26(5).

PMID: 40076864 PMC: 11900495. DOI: 10.3390/ijms26052242.

Choline consumption reduces CVD risk via body composition modification.

Wang H, Lin J, Fan S, Zhang X, Zhou T, Luo R Sci Rep. 2024; 14(1):16152.

PMID: 38997295 PMC: 11245612. DOI: 10.1038/s41598-024-66039-4.

From heart failure and kidney dysfunction to cardiorenal syndrome: TMAO may be a bridge.

Zhang J, Zhu P, Li S, Gao Y, Xing Y Front Pharmacol. 2023; 14:1291922.

PMID: 38074146 PMC: 10703173. DOI: 10.3389/fphar.2023.1291922.

The dietary source of trimethylamine N-oxide and clinical outcomes: an unexpected liaison.

Evans M, Dai L, Avesani C, Kublickiene K, Stenvinkel P Clin Kidney J. 2023; 16(11):1804-1812.

PMID: 37915930 PMC: 10616480. DOI: 10.1093/ckj/sfad095.

Plasma Trimethylamine--Oxide and Incident Ischemic Stroke: The Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis.

Lemaitre R, Jensen P, Wang Z, Fretts A, Sitlani C, Nemet I J Am Heart Assoc. 2023; 12(16):e8711.

PMID: 37581385 PMC: 10492960. DOI: 10.1161/JAHA.122.029230.

References

Miao J, Ling A, Manthena P, Gearing M, Graham M, Crooke R . Flavin-containing monooxygenase 3 as a potential player in diabetes-associated atherosclerosis. Nat Commun. 2015; 6:6498. PMC: 4391288. DOI: 10.1038/ncomms7498. View

Mitchell S, Zhang A, Noblet J, Gillespie S, Jones N, Smith R . Metabolic disposition of [14C]-trimethylamine N-oxide in rat: variation with dose and route of administration. Xenobiotica. 1997; 27(11):1187-97. DOI: 10.1080/004982597239949. View

Gao X, Liu X, Xu J, Xue C, Xue Y, Wang Y . Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet. J Biosci Bioeng. 2014; 118(4):476-81. DOI: 10.1016/j.jbiosc.2014.03.001. View

Ufnal M, Jazwiec R, Dadlez M, Drapala A, Sikora M, Skrzypecki J . Trimethylamine-N-oxide: a carnitine-derived metabolite that prolongs the hypertensive effect of angiotensin II in rats. Can J Cardiol. 2014; 30(12):1700-5. DOI: 10.1016/j.cjca.2014.09.010. View

Tsutsumi Y, Sanui M, Shimojima A, Ishioka H, Urashima M . A cross-sectional study of the association between circulating 25-hydroxyvitamin D levels and predicted operative mortality of patients with cardiovascular disease. J Nutr Sci Vitaminol (Tokyo). 2013; 58(5):327-32. DOI: 10.3177/jnsv.58.327. View

Mente A, Chalcraft K, Ak H, Davis A, Lonn E, Miller R . The Relationship Between Trimethylamine-N-Oxide and Prevalent Cardiovascular Disease in a Multiethnic Population Living in Canada. Can J Cardiol. 2015; 31(9):1189-94. DOI: 10.1016/j.cjca.2015.06.016. View

Al-Waiz M, Mitchell S, Idle J, Smith R . The metabolism of 14C-labelled trimethylamine and its N-oxide in man. Xenobiotica. 1987; 17(5):551-8. DOI: 10.3109/00498258709043962. View

van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal E, de Vos W . Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med. 2013; 368(5):407-15. DOI: 10.1056/NEJMoa1205037. View

Lever M, George P, Slow S, Bellamy D, Young J, Ho M . Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study. PLoS One. 2014; 9(12):e114969. PMC: 4262445. DOI: 10.1371/journal.pone.0114969. View

10.

Teramoto T, Sasaki J, Ueshima H, Egusa G, Kinoshita M, Shimamoto K . Diagnostic criteria for dyslipidemia. Executive summary of Japan Atherosclerosis Society (JAS) guideline for diagnosis and prevention of atherosclerotic cardiovascular diseases for Japanese. J Atheroscler Thromb. 2007; 14(4):155-8. DOI: 10.5551/jat.e537. View

11.

Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K . Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009; 53(6):982-92. DOI: 10.1053/j.ajkd.2008.12.034. View

12.

Wang Z, Tang W, Buffa J, Fu X, Britt E, Koeth R . Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. Eur Heart J. 2014; 35(14):904-10. PMC: 3977137. DOI: 10.1093/eurheartj/ehu002. View

13.

Koeth R, Wang Z, Levison B, Buffa J, Org E, Sheehy B . Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med. 2013; 19(5):576-85. PMC: 3650111. DOI: 10.1038/nm.3145. View

14.

Yancy C, Jessup M, Bozkurt B, Butler J, Casey Jr D, Drazner M . 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013; 128(16):1810-52. DOI: 10.1161/CIR.0b013e31829e8807. View

15.

Hida M, Aiba Y, Sawamura S, Suzuki N, Satoh T, Koga Y . Inhibition of the accumulation of uremic toxins in the blood and their precursors in the feces after oral administration of Lebenin, a lactic acid bacteria preparation, to uremic patients undergoing hemodialysis. Nephron. 1996; 74(2):349-55. DOI: 10.1159/000189334. View

16.

Gallimore A, Godkin A . Epithelial barriers, microbiota, and colorectal cancer. N Engl J Med. 2013; 368(3):282-4. DOI: 10.1056/NEJMcibr1212341. View

17.

Tang W, Wang Z, Fan Y, Levison B, Hazen J, Donahue L . Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol. 2014; 64(18):1908-14. PMC: 4254529. DOI: 10.1016/j.jacc.2014.02.617. View

18.

Vaziri N, Wong J, Pahl M, Piceno Y, Yuan J, DeSantis T . Chronic kidney disease alters intestinal microbial flora. Kidney Int. 2012; 83(2):308-15. DOI: 10.1038/ki.2012.345. View

19.

Tang W, Wang Z, Kennedy D, Wu Y, Buffa J, Agatisa-Boyle B . Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015; 116(3):448-55. PMC: 4312512. DOI: 10.1161/CIRCRESAHA.116.305360. View

20.

Bain M, Faull R, Fornasini G, Milne R, Evans A . Accumulation of trimethylamine and trimethylamine-N-oxide in end-stage renal disease patients undergoing haemodialysis. Nephrol Dial Transplant. 2006; 21(5):1300-4. DOI: 10.1093/ndt/gfk056. View