Association Between Plasma Trimethyllysine and Prognosis of Patients With Ischemic Stroke

Abstract

Background Trimethyllysine, a trimethylamine N‐oxide precursor, has been identified as an independent cardiovascular risk factor in acute coronary syndrome. However, limited data are available to examine the role of trimethyllysine in the population with stroke. We aimed to examine the relationship between plasma trimethyllysine levels and stroke outcomes in patients presenting with ischemic stroke or transient ischemic attack. Methods and Results Data of 10 027 patients with ischemic stroke/transient ischemic attack from the CNSR‐III (Third China National Stroke Registry) and 1‐year follow‐up data for stroke outcomes were analyzed. Plasma levels of trimethyllysine were measured with mass spectrometry. The association between trimethyllysine and stroke outcomes was analyzed using Cox regression models. Mediation analysis was performed to examine the mediation effects of risk factors on the associations of trimethyllysine and stroke outcomes. Elevated trimethyllysine levels were associated with increased risk of cardiovascular death (quartile 4 versus quartile 1: adjusted hazard ratio [HR], 1.72; 95% CI, 1.03–2.86) and all‐cause mortality (quartile 4 versus quartile 1: HR, 1.97; 95% CI, 1.40–2.78) in multivariate Cox regression model. However, no associations were found between trimethyllysine and nonfatal stroke recurrence or nonfatal myocardial infarction. Trimethyllysine was associated with cardiovascular death independent of trimethylamine N‐oxide. Both estimated glomerular filtration rate and hs‐CRP (high‐sensitivity C‐reactive protein) had significant mediation effects on the association of trimethyllysine with cardiovascular death, with a mediation effect of 37.8% and 13.4%, respectively. Conclusions Elevated trimethyllysine level is associated with cardiovascular death among patients with ischemic stroke/transient ischemic attack. Mediation analyses propose that trimethyllysine contributes to cardiovascular death through inflammation and renal function, suggesting a possible pathomechanistic link.

Ischemia preconditioning induces an adaptive response that defines a circulating metabolomic signature in ischemic stroke patients

“…47 The relation between gut microbiota and TIA/AIS is described elsewhere. 48–50 In line with our results. an alteration in the composition of gut microbiota after acute central nervous system injury has been previously described.…”

Residual Risk of Trimethylamine‐N‐Oxide and Choline for Stroke Recurrence in Patients With Intensive Secondary Therapy

“…Plasma levels of TMAO and choline were measured using liquid chromatography–mass spectrometry as in our previous studies. 17 The methods used for TMAO and choline measurement are described in Data S1 and Table S1 and S2 .…”

Effect of TMAO on the incidence and prognosis of cerebral infarction: a systematic review and meta-analysis

“…Furthermore, two studies ( 13 , 24 ) have reported that TMAO is a risk factor for moderate-to-severe cerebral infarction, and an additional study ( 28 ) reported that TMAO is a risk factor for fluctuations in the acute phase of cerebral infarction (finding a 2-point increase in the NIHSS score over 3 days). In addition, four studies ( 12 , 16 , 20 , 23 ) reported a positive correlation between TMAO and a history of cerebral infarction, which further validated the correlation between TMAO and cerebral infarction. All results showed that TMAO influenced the onset, severity, fluctuation, and prognosis of cerebral infarction.…”