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

Abstract

BACKGROUND:

Choline and betaine have been suggested to play a pivotal role in neurotransmitter synthesis, cell membrane integrity, and methyl-group metabolism, exerting neuroprotective effects in patients with various neurological disorders. However, population-based evidence on choline and betaine with subsequent cardiovascular events after stroke is rare.

OBJECTIVES:

We aimed to prospectively investigate the relationships of circulating choline and betaine with cardiovascular events and recurrent stroke in patients with ischemic stroke.

METHODS:

We performed a nested case-control study within the China Antihypertensive Trial in Acute Ischemic Stroke. A total of 323 cardiovascular events (including 264 recurrent strokes) and 323 controls (free of recurrent cardiovascular events) matched for age (±1 y), sex, and treatment group were included. The primary endpoint was a composite of cardiovascular events after ischemic stroke. Plasma choline and betaine were measured at baseline by ultra-high-performance LC-MS/MS. Conditional logistic regression models were applied, and discrimination, reclassification, and calibration of models with choline pathway metabolites were evaluated.

RESULTS:

Plasma choline and betaine were inversely associated with cardiovascular events and recurrent stroke after ischemic stroke. Specifically, in fully adjusted models, each additional SD of choline and betaine was associated with 35% (95% CI: 20%-48%) and 30% (95% CI: 14%-43%) decreased risks of subsequent cardiovascular events, respectively, and 34% (95% CI: 16%-48%) and 29% (95% CI: 12%-43%) decreased risks of recurrent stroke, respectively. In addition, both choline and betaine offered substantial risk discrimination and reclassification improvement for cardiovascular events and recurrent stroke beyond traditional risk factors, as evidenced by an increase in C statistics, the net reclassification index, and integrated discrimination improvement.

CONCLUSIONS:

Plasma choline pathway metabolites, including choline and betaine, were associated with decreased risks of cardiovascular events and recurrent stroke and provided incremental value in risk discrimination and stratification in patients with ischemic stroke. This nested case-control study was based on the China Antihypertensive Trial in Acute Ischemic Stroke, which is registered at clinicaltrials.gov as NCT01840072.

• Authors: Chongke Zhong, Mengyuan Miao, Bizhong Che, Jigang Du, Aili Wang, Hao Peng, Xiaoqing Bu, Jintao Zhang, Zhong Ju, Tan Xu, Jiang He, Yonghong Zhang
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 114 Issue 4 Pg. 1351-1359 (10 04 2021) ISSN: 1938-3207 [Electronic] United States
• PMID: 34159355 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Chemical References

• Lipotropic Agents
• Neuroprotective Agents
• Betaine
• Choline

Topics

• Aged
• Betaine (blood)
• Cardiovascular Diseases (prevention & control)
• Case-Control Studies
• Choline (blood)
• Female
• Humans
• Lipotropic Agents (blood)
• Male
• Middle Aged
• Neuroprotective Agents (blood)
• Recurrence
• Stroke (pathology, prevention & control)