Patients with higher DMG more often used -blockers and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers.

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We evaluated the relationship between plasma dimethylglycine and risk of incident acute myocardial infarction in a large prospective cohort of patients with stable angina pectoris, of whom approximately two thirds were participants in a B-vitamin intervention trial.

Model discrimination and reclassification when adding plasma dimethylglycine to established risk factors were obtained.

We also explored temporal changes and the testretest reliability of plasma dimethylglycine.

Approach and Results Four thousand one hundred fifty patients (72 men; median age 62 years) were included.

Plasma dimethylglycine was associated with several traditional coronary artery disease risk factors.

During a median follow-up of 4.6 years, 343 (8.3) patients experienced an acute myocardial infarction.

The hazard ratio (95 confidence interval) for acute myocardial infarction was 1.95 (1.422.68; P P for interaction0.004, 0.004, and 0.03, respectively).

Plasma dimethylglycine improved discrimination and reclassification and had high testretest reliability.

Conclusions Plasma dimethylglycine is independently related to incident acute myocardial infarction and enhances risk prediction in patients with stable angina pectoris.

Our results motivate further studies on the relationship between 1-carbon metabolism and atherothrombosis.

A potential interplay with lipid and energy metabolism merits particular attention.

BHMT induction has been related to enhanced hepatic apolipoprotein B (apoB) transcription and very low-density lipoprotein excretion, 12 and betaine supplementation in humans has been associated with increased levels of low-density lipoprotein cholesterol in serum.

The G allele of the single nucleotide polymorphism BHMT 742 GA (rs3733890) is related to both higher plasma DMG levels 14 and more extensive coronary artery disease (CAD) in the elderly.

Notably, in a recent, small study of patients with established CAD, plasma DMG was associated with increased risk of all-cause death, acute myocardial infarction (AMI), and hospitalization for heart failure.

This suggests that the flux through BHMT or other determinants of plasma DMG may be related to the development of atherosclerotic CAD.

We also evaluated the improvement in model discrimination and reclassification of patients at risk when adding plasma DMG to a model containing traditional CAD risk factors.

In addition, we studied temporal changes and the testretest variability of plasma DMG.

The findings were reported according to the STrengthening the Reporting of OBservational studies in Epidemiology-Molecular Epidemiology (STROBE-ME) statement.

Materials and Methods Materials and Methods are available in the online-only Supplement.

Results Characteristics of the Study Population According to Quartiles of Plasma DMG Baseline characteristics of the study population are given in Table 1.

The cohort consisted of 72.0 men, and the median (5th95th percentile) age was 62 (4478) years.

Thirty-one percent of the participants were current smokers, 11.8 were diagnosed with diabetes mellitus, 46.7 had hypertension, and 40.3 had a history of previous myocardial infarction.

Patients with valid measurements.

Unadjusted. Adjusted for age and sex.

Median (5th95th percentile) plasma DMG was 4.1 (2.67.3) molL.

Plasma DMG levels were higher in men (4.2 2.77.5 mol) than in women (3.8 2.46.9 molL; P P There was a positive linear relationship between incremental DMG quartiles and age and C-reactive protein, whereas a negative association was observed with estimated glomerular filtration rate (eGFR).

Subjects in higher DMG quartiles more often were smokers, had hypertension and established CVD, whereas plasma DMG was not associated with left ventricular ejection fraction and was only borderline significantly related to the number of stenosed coronary arteries at angiography.

As expected, DMG was strongly related to other 1-carbon metabolites (plasma choline, betaine, tHcy, methionine, and sarcosine), but except for a positive association with plasma methylmalonic acid, there was no relationship between DMG and various markers of B-vitamin status in age- and sex-adjusted analyses.

We further observed an inverse trend between plasma DMG quartiles and total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein A1 levels, whereas there were minor or no associations with other lipid parameters.

Density Of Dmg 1