Plasma Dimethylglycine and Risk of Incident Acute Myocardial Infarction in Patients With Stable Angina Pectoris

Abstract

Objective— Dimethylglycine is linked to lipid metabolism, and increased plasma levels may be associated with adverse prognosis in patients with coronary artery disease. 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 test–retest 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 (1.42–2.68; P <0.001) when comparing plasma dimethylglycine quartile 4 to 1 in a Cox regression model adjusted for age, sex, and fasting status. Adjusting for traditional coronary artery disease risk factors only slightly modified the estimates, which were particularly strong among nonsmokers and among patients with serum triglyceride or apolipoprotein B100 levels ≤median ( P for interaction=0.004, 0.004, and 0.03, respectively). Plasma dimethylglycine improved discrimination and reclassification and had high test–retest 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.

Plasma Cystathionine and Risk of Incident Stroke in Patients With Suspected Stable Angina Pectoris

“…A detailed description of the study population has been published previously 13. In brief, 4164 patients who underwent coronary angiography for suspected stable angina pectoris at Haukeland and Stavanger University Hospitals in Western Norway during 2000–2004 were included.…”

“…Obesity was identified as having body mass index ≥30 kg/m 2 . Current smokers were defined as those who reported currently smoking, those who quit smoking within <1 month preceding examination, or having serum cotinine levels ≥85 nmol/L at baseline 13. Diabetes mellitus included types 1 and 2 and was classified according to previous diagnosis or by having plasma fasting glucose >7 mmol/L, nonfasting glucose >11.1 mmol/L, or a single measurement of glycated hemoglobin >6.5% 17.…”

“…Details on the collection of blood samples and biochemical analyses for relevant clinical indices have been described previously 13. Among patients recruited at Haukeland University Hospital, blood samples were drawn 1 to 3 days before coronary angiography and immediately stored at −80°C, whereas such samples from patients at Stavanger University Hospital were drawn after the angiographic procedure and subsequently transported within 48 hours to the core laboratory, until separated and frozen at −80°C.…”

“…Plasma cystathionine had within‐day coefficient of variation of ≤1.8% and between‐day coefficient of variation of ≤3.6%. Serum apolipoprotein A1, apolipoprotein B, and C‐reactive protein (CRP) were measured as previously described 13. Low‐density lipoprotein cholesterol and estimated glomerular filtration rate (eGFR) were calculated using the Friedewald and Chronic Kidney Disease Epidemiology Collaboration formula, respectively.…”

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

“…No associations of dietary choline and betaine with cardiovascular disease (CVD) risk have been reported,7, 8, 9 whereas circulating choline and its metabolites have been associated with lifestyle diseases including atherosclerotic cardiovascular disease 4, 6, 10, 11. However, less attention has been paid to the possible associations between choline metabolites and cardiac arrhythmias, although a recent metabolomics study suggested no significant association between plasma betaine and incident AF in the population‐based Framingham Study 12…”