Plasma choline and betaine and risks of cardiovascular events and recurrent stroke after ischemic stroke

Zhong, Chongke; Miao, Mengyuan; Che, Bizhong; Du, Jigang; Wang, Aili; Peng, Hao; Bu, Xiaoqing; Zhang, Jintao; Ju, Zhong; Xu, Tan; He, Jiang; Zhang, Yonghong

doi:10.1093/ajcn/nqab199

Cited by 16 publications

(16 citation statements)

References 37 publications

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“…However, result of a case–control study from Chinese patients indicated that plasma choline was inversely associated with recurrent stroke in the setting of ischemic stroke. 19 In the present study, we observed that elevated plasma levels of TMAO and choline were associated with an increased risk of recurrent stroke in the cohort of CNSR‐III, which is a nationwide prospective registry for patients presenting to hospitals with acute ischemic cerebrovascular events.…”

Section: Discussionmentioning

confidence: 49%

“…Although some studies have also investigated the association of TMAO and choline with stroke recurrence in the secondary prevention population of ischemic stroke, the results are not consistent. 5 , 18 , 19 Haghikia et al 5 demonstrated that patients with elevated TMAO levels, but not choline, were at higher risk of recurrent stroke over 1‐year follow‐up. However, result of a case–control study from Chinese patients indicated that plasma choline was inversely associated with recurrent stroke in the setting of ischemic stroke.…”

Section: Discussionmentioning

confidence: 99%

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

Xue

Zhao

et al. 2022

JAHA

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Background Trimethylamine N‐oxide (TMAO) contributes to cardiovascular disease through its prothrombotic, proatherothrombotic, and proinflammatory effects. We aimed to evaluate whether residual risk of recurrent stroke of TMAO and its precursor choline remain among patients who received dual‐antiplatelet therapy and intensive lipid‐lowering therapy and with a low inflammation level (high‐sensitivity C‐reactive protein <2 mg/L on admission). Methods and Results 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 1 year. Multivariable‐adjusted hazard ratios were calculated using Cox regression models to investigate the associations of TMAO and choline with stroke recurrence. 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 <2 mg/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 <2 mg/L (3.57 [95% CI, 1.73–7.38]; and 2.19 [95% CI, 1.16–4.16], respectively). Conclusions TMAO and choline were risk factors for recurrent stroke independent of dual‐antiplatelet therapy, intensive lipid‐lowering therapy at discharge, and low inflammation on admission.

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Section: Discussionmentioning

confidence: 49%

Section: Discussionmentioning

confidence: 99%

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

Xue

Zhao

et al. 2022

JAHA

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“…Additionally, choline deficiency increases the activity of acetylcholinesterase ( 21 ), and serum cholinesterase activities reflect the intensity of the neuroinflammatory response in patients with stroke ( 22 ). Moreover, choline and betaine are metabolites of the choline pathway associated with decreased cardiovascular risks and recurrent strokes ( 23 , 24 ).…”

Section: Discussionmentioning

confidence: 99%

“…Betaine is an oxidation product of choline, which is linked to folate and serves as a methyl donor in one-carbon metabolism ( 12 , 14 , 25 ). A low concentration of betaine is associated with a number of stroke risk factors, such as insulin resistance, diabetes mellitus, lipid metabolism, and atherogenic dyslipidemia ( 24 , 26 – 28 ). In the current study, we observed an inverse relationship between betaine and risk of MMD and its subtypes.…”

Section: Discussionmentioning

confidence: 99%

Circulating choline pathway nutrients and risk of moyamoya disease

Zhao

Zhai

et al. 2022

Front. Nutr.

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BackgroundCirculating choline pathway nutrients play a critical role in first stroke and recurrent stroke. However, there is limited information available on the effects of choline pathway nutrients on the risk of moyamoya disease (MMD) and its subtypes. We investigated the association between circulating choline and betaine and the incident risk of MMD and its subtypes.MethodsThe case-control study enrolled 385 patients with MMD [i.e., 110 transient ischemic attack (TIA)-type MMD, 157 infarction-type MMD, and 118 hemorrhagic-type MMD] and 89 matched healthy controls.ResultsSerum choline and betaine were inversely related to the risk of MMD and its subtypes. The risk of MMD was decreased with each increment in choline level [per 1 μmol increase: odds ratio (OR), 0.756; 95% CI, 0.678–0.843] and betaine level (per 1 μmol increase: OR, 0.952; 95% CI, 0.932–0.972), respectively. When choline and betaine were assessed as quartiles, compared with the lowest quartile of serum choline and betaine levels, those in the highest quartile had a significantly decreased risk of MMD (choline, Q4 vs. Q1: OR, 0.023; 95% CI, 0.005–0.118; betaine, Q4 vs. Q1: OR, 0.058; 95% CI, 0.018–0.184).ConclusionsSerum choline and betaine were associated with the decreased risk of MMD and its subtypes.

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“…The sample preparation for measurements of plasma carnitine, choline, betaine, TML, TMAO, and cotinine (a biomarker of recent nicotine exposure) has been mentioned by a previous report [27]. These metabolites were measured by an ultrahigh performance liquid chromatography–tandem mass spectrometry platform [28].…”

Section: Methodsmentioning

confidence: 99%

Associations of plasma TMAO and its precursors with stroke risk in the general population: A nested case‐control study

Liu

Zhou

et al. 2022

J Intern Med

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Background. Trimethylamine N-oxide (TMAO) is a gut-derived atherogenic metabolite. However, the role of TMAO and its precursors in the development of stroke remains unclear. We aimed to examine the associations between metabolites in TMAO biosynthesis and stroke risk. Methods.A nested case-control study was performed in a community-based cohort (2013-2018, n = 16,113). We included 412 identified stroke cases and 412 controls matched by age and sex. Plasma carnitine, choline, betaine, trimethyl lysine (TML), and TMAO were measured by ultrahigh performance liquid chromatographytandem mass spectrometry. Conditional logistic regression analyses were used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs) between these biomarkers and stroke risk.Results. After adjustment for body mass index, smoking, hypertension, educational attainment, and estimated glomerular filtration rate, the corresponding OR for the highest versus lowest quartile was 1.74 (95% CI: 1.16-2.61, P trend = 0.006) for total stroke and 1.81 (95% CI: 1.14-2.86, P trend = 0.020) for ischemic stroke in an essentially linear dose-response fashion. A significant association between TMAO and nonischemic stroke was shown as a J-shape with OR for the highest versus second quartile of 5.75 (95% CI: 1.73-19.1). No meaningful significant risk association was found among plasma carnitine, choline, betaine, and TML with stroke risk.Conclusions. Increased TMAO was associated with higher stroke risk in the community-based population, whereas the TMAO precursors carnitine, choline, betaine, and TML were not associated. Further studies are warranted to confirm these findings and to further elucidate the role of TMAO in the development of stroke.

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Plasma choline and betaine and risks of cardiovascular events and recurrent stroke after ischemic stroke

Cited by 16 publications

References 37 publications

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

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

Circulating choline pathway nutrients and risk of moyamoya disease

Associations of plasma TMAO and its precursors with stroke risk in the general population: A nested case‐control study

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