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Updated: Nov 10, 2025
Author Spotlight: Assessing Ischemic Stroke Damage Through Middle Cerebral Artery Occlusion Model
Published on: August 11, 2023
Trimethyllysine, vascular risk factors and outcome in acute ischemic stroke (MARK-STROKE)
Edzard Schwedhelm1,2, Mirjam von Lucadou3,4, Sven Peine5
1Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany. schwedhelm@uke.de.
Abstract:
Trimethyllysine (TML) is involved in the generation of the pro-atherogenic metabolite trimethylamine-N-oxide (TMAO) by gut microbiota. In clinical studies, elevated TML levels predicted major adverse cardiovascular events (MACE) in patients with acute or stable coronary artery disease (CAD). In contrast to cardiovascular patients, the role of TML in patients with acute cerebral ischemia is unknown. Here, we evaluated circulating TML levels in 374 stroke patients from the prospective biomarkers in stroke (MARK-STROKE) study. Compared with 167 matched healthy controls, acute ischemic stroke patients had lower median TML plasma concentrations, i.e. 0.71 vs. 0.47 µmol/L (p < 0.001) and this difference persisted after adjusting for age and sex. TML plasma concentrations were associated with age, serum creatinine, glucose, cholesterol and lysine. Patients with prevalent arterial hypertension, atrial fibrillation or a history of myocardial infarction had increased TML levels, but this observation was not independent of age, sex and GFR. In 274 patients, follow-up data were available. During a median follow-up of 284 [25th-75th percentile: 198, 431] days, TML was not associated with incident MACE (stroke, myocardial infarction, death). In summary, our data suggests a different role of TML in acute ischemic stroke compared with CAD patients.
Insights
Trimethyllysine (TML) levels were lower in acute ischemic stroke patients compared to healthy individuals. TML did not predict major adverse cardiovascular events in stroke patients during follow-up.
Area of Science:
- Biochemistry
- Cardiovascular Research
- Neurology
Background:
- Trimethyllysine (TML) is a precursor to trimethylamine-N-oxide (TMAO), a pro-atherogenic metabolite produced by gut microbiota.
- Elevated TML levels have been linked to major adverse cardiovascular events (MACE) in coronary artery disease (CAD) patients.
- The role of TML in acute ischemic stroke remains unexplored.
Purpose of the Study:
- To investigate circulating TML levels in patients with acute ischemic stroke.
- To determine if TML is associated with MACE in stroke patients.
Main Methods:
- Analysis of plasma TML concentrations in 374 acute ischemic stroke patients and 167 healthy controls from the MARK-STROKE study.
- Assessment of TML association with clinical factors and follow-up data for incident MACE over a median of 284 days.
Main Results:
- Acute ischemic stroke patients exhibited significantly lower median TML plasma concentrations (0.47 µmol/L) compared to healthy controls (0.71 µmol/L).
- TML levels correlated with age, creatinine, glucose, cholesterol, and lysine, and were higher in patients with hypertension, atrial fibrillation, or prior myocardial infarction, but not independently.
- TML was not associated with incident MACE in stroke patients during the follow-up period.
Conclusions:
- Circulating TML levels are lower in acute ischemic stroke patients compared to healthy individuals, suggesting a distinct role in stroke versus CAD.
- TML does not appear to be a predictor of future major adverse cardiovascular events in the context of acute ischemic stroke.
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