Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Residual Risk of Trimethylamine-N-Oxide and Choline for Stroke Recurrence in Patients With Intensive Secondary Therapy
First author：Jing Xue
Corresponding author：Yongjun Wang
essential_information
2022-10-04
Published articles
Journal：Journal of the American heart association
Publication type: Article
IF(IF): 6.106
PMID: 36193936 Link To Pubmed Full text Download
Background And Purpose
Evidence from The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial and Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial have demonstrated that dual antiplatelet therapy could reduce the risk of major ischemic events without increasing the risk of major hemorrhage in patients with minor stroke or transient ischemic attack. Evidence form The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial and Treat Stroke to Target (TST) trial have shown that lipid-lowering therapy could reduce the major vascular event with no increase in intracranial hemorrhage. Evidence from the Canakinumab Anti-Inflammatory Thrombosis Outcome Study (CANTOS) and the Low Dose Colchicine (LoDoCo) trial for secondary prevention of cardiovascular disease have demonstrated the clinical benefit of a targeted anti-inflammatory therapy. However, residual risk of stroke recurrence persists in patients adhere to antiplatelet therapy and with controlled LDL-cholesterol and hsCRP, suggesting that there may be other risk factors contributed to the residual risk of stroke recurrence. We aimed to estimate potential factors which could further reduce the residual risk of recurrent stroke, when dual antiplatelet therapy have applied, and LDL-C and inflammatory are kept at low level.
Method
Patients with ischemic stroke or transient ischemic attack were enrolled from the CNSR-III (Third China National Stroke Registry) in China. Plasma TMAO and choline concentrations at baseline were measured in 9793 participants using liquid chromatography–mass spectrometry. The primary outcome was a new stroke within 1year. Multivariable-adjusted hazard ratios were calculated using Cox regression models to investigate the associations of TMAO and choline with stroke recurrence.
Conclusion
TMAO and choline were risk factors for recurrent stroke independent of dual-antiplatelet therapy, intensive lipidlowering therapy at discharge, and low inflammation on admission.
Main results
Among all patients, elevated TMAO and choline levels were associated with an increased risk of recurrent stroke (adjusted hazard ratios, 1.28 [95% CI, 1.12–1.45]; and 1.50 [95% CI, 1.32–1.71], respectively). Moreover, elevated TMAO and choline levels were associated with an increased risk of recurrent stroke among patients who received dual-antiplatelet therapy (1.65 [95% CI, 1.28–2.13]; and 1.70 [95% CI, 1.32–2.19], respectively), intensive lipid-lowering therapy (1.49 [95% CI, 1.15–1.94]; and 1.49 [95% CI, 1.15–1.92], respectively), with high-sensitivity C-reactive protein <2mg/L (1.39 [95% CI, 1.14–1.69]; and 1.88 [95% CI, 1.53–2.30], respectively), and concurrently received dual-antiplatelet therapy, intensive lipid-lowering therapy and with high-sensitivity C-reactive protein <2mg/L (3.57 [95% CI, 1.73–7.38]; and 2.19 [95% CI, 1.16–4.16], respectively).