Abstract Body: Background
Trimethylamine N-oxide (TMAO), a gut microbiome-derived metabolite trimethylamine-containing nutrients, is mechanistically linked to atherosclerosis progression and platelet aggregation, leading to cardiovascular disease. Recent studies have showed that TMAO levels are elevated in patients with ischemic stroke; however, its association with heterogenous pathophysiology of stroke remains unknown. In this study, we aimed to investigate what stroke subtypes plasma TMAO levels were associated with.
Methods
The study was prospectively conducted at a single center in Japan between 2021 and 2022, enrolling acute stroke patients and non-stroke subjects. Blood samples were collected at the first post-hospitalization or during a medical checkup after obtaining written informed consent. Plasma TMAO levels were measured using liquid chromatography-mass spectrometry. We compared TMAO levels between acute stroke patients and non-stroke subjects, as well as among stroke subtypes.
Results
We enrolled 162 stroke patients (median age, 74) and 50 non-stroke subjects (75). Plasma TMAO levels were significantly higher in stroke patients than in non-stroke subjects (median [Interquartile range]: 3.0 [1.1–7.7] vs. 2.1 [0.8–4.2] µM, p = 0.01), and high TMAO levels (TMAO > 5.0 µM) distinguished stroke patients from non-stroke subjects (odds ratio 1.20, 95%CI 1.06-1.36, p < 0.01). High TMAO levels were independently associated with stroke after adjusted for age, sex, and conventional vascular risk factors (adjusted odds ratio 1.14, 95% confidence interval [CI] 1.01–1.28, p < 0.05). The proportion of patients with elevated TMAO levels was significantly higher in patients with cardioembolic stroke (11/34 [32%]), large-artery atherosclerosis (11/28 [39%]), small-vessel occlusion (11/36 [31%]), and hypertensive intracerebral hemorrhage (15/43 [35%]) than in non-stroke subjects (7/50 [14%]) (p < 0.05), but did not differ between patients with cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (1/9 [11%]) and non-stroke subjects (p = 0.9).
Conclusions
High plasma TMAO levels were significantly associated with hypertensive intracerebral hemorrhage as well as with each ischemic stroke type, but not with CAA-related intracerebral hemorrhage, suggesting that TMAO may confer a risk for stroke via the development of atherosclerosis.