Betaine and Secondary Events in an Acute Coronary Syndrome Cohort

Lever, Michael; George, Peter M.; Elmslie, Jane; Atkinson, Wendy; Slow, Sandy; Molyneux, Sarah L.; Troughton, Richard W.; Richards, A. Mark; Frampton, Christopher M.; Chambers, Stephen T.

doi:10.1371/journal.pone.0037883

Cited by 68 publications

(69 citation statements)

References 52 publications

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“…Svingen et al 7 also reported a high coefficient of reliability (0.93) for plasma DMG in people with stable angina. Plasma DMG was also shown to be predictive of secondary cardiovascular events, 7 which is in agreement with the findings of Lever et al 6 The predictive value of single Median values were calculated from all four time points. The coefficients of reliability for the urine results were calculated on log-transformed data because the data were not normally distributed.…”

Section: Individualitysupporting

confidence: 87%

“…3 Urinary betaine excretion is often elevated in diabetes and renal failure. 4,5 Plasma betaine concentrations and urinary betaine excretions can predict secondary cardiovascular events in people with established vascular disease, 6 and the plasma concentration of dimethylglycine, the product of betaine metabolism, is an especially strong prognostic marker. 6,7 These predictions are stronger for patients with diabetes.…”

Section: Introductionmentioning

confidence: 99%

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Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period

et al. 2014

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Background: Plasma betaine concentrations and urinary betaine excretions have high test-retest reliability. Abnormal betaine excretion is common in diabetes. We aimed to confirm the individuality of plasma betaine and urinary betaine excretion in an overweight population with type 2 diabetes and compare this with the individuality of other osmolytes, onecarbon metabolites and trimethylamine-N-oxide (TMAO), thus assessing their potential usefulness as disease markers. Methods: Urine and plasma were collected from overweight subjects with type 2 diabetes at four time points over a two-year period. We measured the concentrations of the osmolytes: betaine, glycerophosphorylcholine (GPC) and taurine, as well as TMAO, and the one-carbon metabolites, N,N-dimethylglycine (DMG) and free choline. Samples were measured using tandem mass spectrometry (LC-MS/MS). Results: Betaine showed a high degree of individuality (or test-retest reliability) in the plasma (index of individuality ¼ 0.52) and urine (index of individuality ¼ 0.45). Betaine in the plasma had positive and negative log-normal reference change values (RCVs) of 54% and À35%, respectively. The other osmolytes, taurine and GPC were more variable in the plasma of individuals compared to the urine. DMG and choline showed high individuality in the plasma and urine. TMAO was highly variable in the plasma and urine (log-normal RCVs ranging from 403% to À80% in plasma). Conclusions: Betaine is highly individual in overweight people with diabetes. Betaine, its metabolite DMG, and precursor choline showed more reliability than the osmolytes, GPC and taurine. The low reliability of TMAO suggests that a single TMAO measurement has low diagnostic value.

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Section: Individualitysupporting

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period

et al. 2014

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“…A cross‐sectional analysis in HUSK suggested that high choline and low betaine plasma concentrations were associated with an unfavorable cardiovascular risk profile 31. A study among patients with established coronary heart disease reported that both high and low plasma betaine concentrations were associated with an increased risk of later coronary events and hospitalization for heart failure 32. In WENBIT patients with stable angina pectoris, elevated plasma choline levels were associated with an increased risk of acute myocardial infarction in nonsmoking patients 6…”

Section: Discussionmentioning

confidence: 99%

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

Zuo

Svingen

Tell

et al. 2018

JAHA

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BackgroundAlthough choline metabolism has been associated with atherosclerotic heart disease, less research attention has been paid to the associations of choline and its oxidative metabolite betaine with cardiac arrhythmias.Methods and ResultsWe evaluated associations of plasma concentrations and dietary intakes of choline and betaine with long‐term atrial fibrillation (AF) risk in a community‐based cohort, HUSK ([the Hordaland Health Study] n=6949), and validated the findings in 2 patient cohorts: the Western Norway Coronary Angiography Cohort (n=4164) and the NORVIT (Norwegian B‐Vitamin) Trial (n=3733). Information on AF was obtained from the CVDNOR (Cardiovascular Disease in Norway) project. In HUSK, WECAC (Western Norway Coronary Angiography Cohort), and NORVIT, 552, 411, and 663 AF cases were identified during a median follow‐up time of 10.9, 7.3, and, 8.7 years, respectively. Plasma concentrations of choline and betaine were significantly positively associated with later AF risk after multivariable adjustments in HUSK. Such associations were independently replicated in the 2 external prospective patient cohorts. The pooled hazard ratio was 1.13 (95% confidence interval 1.08‐1.19, P<0.001) and 1.16 (95% confidence interval 1.10‐1.22, P<0.001) per SD increment for log‐transformed choline and betaine, respectively. Moreover, dietary intake of choline was marginally associated with AF risk (pooled hazard ratio 1.29, 95% confidence interval 1.01‐1.66, fifth versus first quintile), whereas no significant association was observed between dietary betaine and AF risk.ConclusionsOur findings indicate that plasma concentrations as well as dietary intake of choline, but not betaine, are associated with subsequent risk of AF, suggesting a potential role of choline metabolism in the pathogenesis of AF.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov.Unique identifier: NCT00671346.

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“…In addition, the NAME population consisted of community-dwelling elders in contrast with patient populations who have been studied by other authors. For example, a study of a cohort with acute coronary syndrome concluded that high and low plasma betaine concentrations were associated with increased risks of secondary heart failure and acute myocardial infarction, respectively (24). A second study in the same cohort concluded that lower plasma betaine concentrations were associated with higher concentrations of triglycerides and non-HDL cholesterol (25).…”

Section: Discussionmentioning

confidence: 99%

Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults,

Roe

Zhang

Bhadelia

et al. 2017

The American Journal of Clinical Nutrition

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Background: There is a potential role of choline in cardiovascular and cerebrovascular disease through its involvement in lipid and one-carbon metabolism. Objective: We evaluated the associations of plasma choline and choline-related compounds with cardiometabolic risk factors, history of cardiovascular disease, and cerebrovascular pathology. Design: A cross-sectional subset of the Nutrition, Aging, and Memory in Elders cohort who had undergone MRI of the brain (n = 296; mean 6 SD age: 73 6 8.1 y) was assessed. Plasma concentrations of free choline, betaine, and phosphatidylcholine were measured with the use of liquid-chromatography-stable-isotope dilutionmultiple-reaction monitoring-mass spectrometry. A volumetric analysis of MRI was used to determine the cerebrovascular pathology (white-matter hyperintensities and small-and large-vessel infarcts). Multiple linear and logistic regression models were used to examine relations of plasma measures with cardiometabolic risk factors, history of cardiovascular disease, and radiologic evidence of cerebrovascular pathology. Results: Higher concentrations of plasma choline were associated with an unfavorable cardiometabolic risk-factor profile [lower highdensity lipoprotein (HDL) cholesterol, higher total homocysteine, and higher body mass index (BMI)] and greater odds of large-vessel cerebral vascular disease or history of cardiovascular disease but lower odds of small-vessel cerebral vascular disease. Conversely, higher concentrations of plasma betaine were associated with a favorable cardiometabolic risk-factor profile [lower low-density lipoprotein (LDL) cholesterol and triglycerides] and lower odds of diabetes. Higher concentrations of plasma phosphatidylcholine were associated with characteristics of both a favorable cardiometabolic risk-factor profile (higher HDL cholesterol, lower BMI, lower C-reactive protein, lower waist circumference, and lower odds of hypertension and diabetes) and an unfavorable profile (higher LDL cholesterol and triglycerides). Conclusion: Choline and its metabolites have differential associations with cardiometabolic risk factors and subtypes of vascular disease, thereby suggesting differing roles in the pathogenesis of cardiovascular and cerebral large-vessel disease compared with that of small-vessel disease.Am J Clin Nutr 2017;105:1283-90.

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Betaine and Secondary Events in an Acute Coronary Syndrome Cohort

Cited by 68 publications

References 52 publications

Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period

Variation of betaine, N,N-dimethylglycine, choline, glycerophosphorylcholine, taurine and trimethylamine-N-oxide in the plasma and urine of overweight people with type 2 diabetes over a two-year period

Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles

Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults,

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