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. 2012;7(5):e37883.
doi: 10.1371/journal.pone.0037883. Epub 2012 May 23.

Betaine and secondary events in an acute coronary syndrome cohort

Michael Lever  1 , Peter M George, Jane L Elmslie, Wendy Atkinson, Sandy Slow, Sarah L Molyneux, Richard W Troughton, A Mark Richards, Christopher M Frampton, Stephen T Chambers
Affiliations

Betaine and secondary events in an acute coronary syndrome cohort

Michael Lever et al. PLoS One. 2012.

Abstract

Background: Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients.

Methods: Plasma (531) and urine (415) samples were collected four months after discharge following an acute coronary event. Death (34), secondary acute myocardial infarction (MI) (70) and hospital admission for heart failure (45) events were recorded over a median follow-up of 832 days.

Principal findings: The highest and lowest quintiles of urinary betaine excretion associated with risk of heart failure (p = 0.0046, p = 0.013 compared with middle 60%) but not with subsequent acute MI. The lowest quintile of plasma betaine was associated with subsequent acute MI (p = 0.014), and the top quintile plasma betaine with heart failure (p = 0.043), especially in patients with diabetes (p<0.001). Top quintile plasma concentrations of dimethylglycine (betaine metabolite) and top quintile plasma homocysteine both associated with all three outcomes, acute MI (p = 0.004, <0.001), heart failure (p = 0.027, p<0.001) and survival (p<0.001, p<0.001). High homocysteine was associated with high or low betaine excretion in >60% of these subjects (p = 0.017). Median NT-proBNP concentrations were lowest in the middle quintile of plasma betaine concentration (p = 0.002).

Conclusions: Betaine insufficiency indicates increased risk of secondary heart failure and acute MI. Its association with elevated homocysteine may partly explain the disappointing results of folate supplementation. In some patients, especially with diabetes, elevated plasma betaine also indicates increased risk.

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Conflict of interest statement

Competing Interests: No competing interests exist. The host institution for this work was Canterbury Health Laboratories, the laboratory service of Christchurch Hospital, a public hospital that is affiliated with the University of Otago School of Medicine.

Figures

Figure 1
Figure 1. Betaine metabolism.
Metabolic pathways involving betaine. BHMT: betaine homocysteine methyltransferase, a zinc metalloenzyme abundant in human liver and kidney tissues. SAM: S-adenosylmethionine, ubiquitous methyl-group donor in human metabolism.
Figure 2
Figure 2. Outcomes in quintiles.
Kaplan-Meier curves for time to first secondary event after samples taken: A & B: quintiles of gender-adjusted plasma betaine concentrations, A without acute MI, B without admission to hospital for heart failure; C & D: quintiles of plasma homocysteine concentrations, C without acute MI, D without admission to hospital for heart failure. Significance based on log-rank statistic for paired comparisons.
Figure 3
Figure 3. Effect of diabetes.
Kaplan-Meier curves for time to first secondary events after samples taken: A & B subjects without diabetes, A time without acute MI, B time without admission to hospital with heart failure; C & D subjects with diabetes, C time without acute MI, D time without admission to hospital with heart failure. Quintiles (based on whole population) of gender-adjusted plasma betaine concentrations. Significance based on log-rank statistic for paired comparisons.
Figure 4
Figure 4. NT-proBNP and plasma betaine.
Median NT-proBNP concentrations of deciles of gender-corrected plasma betaine concentrations; trend (quadratic regression) and 95% confidence intervals shown (p<0.001).
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