Trimethylamine N-oxide is associated with coronary atherosclerotic burden in non-ST-segment myocardial infarction patients: SZ-NSTEMI prospective cohort study

Abstract

Trimethylamine N-oxide (TMAO) is reported to accelerate atherosclerosis and the development of adverse cardiac outcomes. Relationship between coronary atherosclerotic burden and TMAO has been examined in stable coronary artery disease and ST-segment elevation myocardial infarction, but not in non-ST-segment elevation myocardial infarction (NSTEMI). We examined the association between TMAO and coronary atherosclerotic burden in NSTEMI. In this prospective cohort study, two groups including NSTEMI (n = 73) and age-sex matched Healthy (n = 35) individuals were enrolled between 2019 and 2020. Coronary atherosclerotic burden was stratified based on the number of diseased coronary vessels and clinical risk scores including SYNTAX and GENSINI. Fasting plasma TMAO was measured by isotope dilution high-performance liquid chromatography. The median plasma TMAO levels were significantly higher in the NSTEMI group than in the Healthy group, respectively (0.59 μM; interquartile range [IQR]: 0.43-0.78 versus 0.42 μM; IQR: 0.33-0.64; P = 0.006). Within the NSTEMI group, higher TMAO levels were observed in the multivessel disease (MVD) versus single vessel disease (P = 0.002), and intermediate-high risk (score ≥ 23) versus low risk (score < 23) of SYNTAX (P = 0.003) and GENSINI (P = 0.005). TMAO level remained an independent predictor of MVD (odds ratio [OR]: 5.94, P = 0.005), intermediate-high risk SYNTAX (OR: 3.61, P = 0.013) and GENSINI scores (OR: 4.60, P = 0.008) following adjustment for traditional risk factors. Receiver operating characteristic curve (AUC) analysis for TMAO predicted MVD (AUC: 0.73, 95% confidence interval [Cl]: 0.60-0.86, P = 0.002), intermediate-high SYNTAX score (AUC: 0.70, 95% Cl: 0.58-0.82, P = 0.003) and GENSINI score (AUC: 0.70, 95% Cl: 0.57-0.83, P = 0.005). In all, TMAO levels are independently associated with high coronary atherosclerotic burden in NSTEMI.

Atherosclerotic patients with diabetes mellitus may break through the threshold of healthy TMAO levels formed by long-term statins therapy

“…Although metformin has similar efficacy on TMAO lowering [ 33 ], only 5% of subjects in our cohort received this drug, which not enough to explain the overall level decrease of TMAO in our cohort. Similar drug regimens were also reported in the previous atherosclerosis associated TMAO studies in Han Chinese population [ 34 , 35 ]. Waleed et al recruited 73 newly diagnosed 18–75 aged non-ST-segment elevation MI patients during 2019–2020, giving aspirin and clopidogrel antiplatelet therapy to them, and their plasma TMAO levels were detected as 0.42–0.78 μM (appr.…”

“…Waleed et al recruited 73 newly diagnosed 18–75 aged non-ST-segment elevation MI patients during 2019–2020, giving aspirin and clopidogrel antiplatelet therapy to them, and their plasma TMAO levels were detected as 0.42–0.78 μM (appr. 31–58 ng/mL) [ 34 ]. Sheng et al recruited 335 newly diagnosed ≥18 aged ST-segment elevation MI patients during 2017–2018, giving aspirin and ticagrelor or clopidogrel therapy to them, and their plasma TMAO levels were detected as 1.34–3.90 μM (appr.…”

Influence of Gut Microbiota and Trimethylamine <i>N</i>-Oxide in Patients with Coronary Heart Disease

“…The results of the current study are similar to Waleed's study results in 2020. 12) In addition, a study conducted by Li, et al revealed that the TMAO level in acute coronary syndromes was an independent predictor of both short-term (30 days and 6 months) and long-term (7 years) major adverse cardiac events. 13) However, in a large cohort of 2,529 CKD patients, subjects with higher levels of TMAO were independently associated with an increased risk of cardiovascular events.…”

Alterations in trimethylamine-N-oxide in response to Empagliflozin therapy: a secondary analysis of the EMMY trial

“…Clinical and epidemiological studies also suggest a strong association between elevated TMAO levels and adverse CVD outcomes in patients with acute cardiovascular manifestations. For example, elevated plasma TMAO levels have been associated with an increased risk of short- and long-term major adverse cardiovascular events (MACE) in patients with acute coronary syndrome and myocardial infarction [ 7 – 10 ]. TMAO has been correlated with a high coronary atherosclerotic burden of ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI) [ 11 – 13 ], and plaque rupture in STEMI patients [ 14 ].…”