G.F.T. Svingen

Elevated plasma dimethylglycine is a risk marker of mortality in patients with coronary heart disease

Aim To investigate whether plasma dimethylglycine was associated with and improved risk prediction of mortality among patients with coronary heart disease (CHD). Methods By Cox modelling, we explored the association between plasma dimethylglycine and mortality in two independent cohorts of patients with suspected stable angina pectoris (SAP) (n = 4156) and acute myocardial infarction (AMI) (n = 3733). We also assessed any improvement in risk prediction by adding plasma dimethylglycine to established CHD risk factors. Results Median follow-up time was 4.7 and 7.0 years among patients with SAP and AMI, respectively. Across both cohorts, elevated plasma dimethylglycine levels were linearly associated with increased risk of all-cause mortality (age and gender adjusted hazard ratios (95% confidence interval, CI) were 1.72 (1.21–2.46) and 1.76 (1.42–2.18) when comparing the fourth versus the first plasma dimethylglycine quartile in patients with SAP and AMI, respectively). There was a particularly strong risk association between plasma dimethylglycine and cardiovascular, as compared with non-cardiovascular, mortality (age and gender adjusted hazard ratios (95% CI) 1.94 (1.21–3.11) and 1.43 (0.83–2.47) among patients with SAP and 1.97 (1.50–2.59) and 1.44 (1.02–2.04) among patients with AMI, respectively). The relationship between dimethylglycine and all-cause and cardiovascular mortality was only slightly attenuated in analyses adjusted for established CHD risk factors. Plasma dimethylglycine also improved risk prediction for all-cause and cardiovascular mortality, and especially among patients with AMI. Conclusions Elevated plasma dimethylglycine was associated with and improved risk prediction of mortality in patients with suspected or verified CHD. This relationship was stronger for death from cardiovascular, as compared with non-cardiovascular, causes.

Plasma choline, smoking, and long-term prognosis in patients with stable angina pectoris

Background Plasma choline has been associated with cardiovascular disease and nonalcoholic steatohepatitis. Design We sought to study relations of plasma choline and its metabolite betaine to long-term risk of acute myocardial infarction (AMI) and all-cause mortality according to smoking status, in patients undergoing coronary angiography for stable angina pectoris. Methods Samples were obtained before angiography from 2568 patients who were subsequently randomized in the Western Norway B-Vitamin Intervention Trial (WENBIT). Hazard ratios (HR) were calculated using multivariate Cox-regression and p-values were reported for trends over quartiles. Results Plasma concentrations of choline, but not betaine, were lower in smokers, and choline was positively associated with C-reactive protein and troponin T in nonsmokers, but not in smokers (p for interaction <0.03). During a follow up of 4.8 ± 1.4 (mean ± SD) years, 8.3% suffered from AMI and 6.1% died. In the total population, choline was not associated with AMI or all-cause mortality. However, comparing the highest vs. the lowest quartiles, plasma choline was associated with increased risk of AMI in nonsmokers (HR 2.63, 95% CI 1.56 to 5.51; p for trend = 0.013) and no risk in smokers (p for interaction < 0.001). Plasma choline significantly improved discrimination and reclassification when added to established cardiovascular risk factors. Plasma betaine was not associated with either endpoint. Conclusions In patients with stable angina pectoris, elevated plasma choline is associated with elevated troponin levels and increased risk of AMI in nonsmokers. These results motivate further research into the relation between choline metabolism, smoking, and atherothrombosis.

The risk association of plasma total homocysteine with acute myocardial infarction is modified by serum vitamin A

Background Plasma total homocysteine (tHcy) has been implicated in the development of cardiovascular disease, but the mechanisms remain unclear. Vitamin A (Vit-A) is involved in homocysteine metabolism and we therefore explored the potential interaction between plasma tHcy and serum Vit-A in relation to incident acute myocardial infarction. Methods Cox proportional hazards models were used to assess the prospective relationships between tHcy and acute myocardial infarction in 2205 patients from Western Norway undergoing elective coronary angiography for suspected stable angina pectoris. Results are reported as hazard ratio per standard deviation increase in log-transformed tHcy. An interaction term for tHcy × Vit-A was added to multivariate models including age, sex, smoking, apolipoprotein B fasting, statin and aspirin prescription and estimated glomerular filtration rate. Results Geometric mean (geometric standard deviation) age of the participants (64.3% men) was 62.3 (1.24) years. Plasma tHcy was higher among participants in the upper versus lower Vit-A tertile. During 7 (2.4) years of follow-up, 15.1% suffered an AMI. A significant association of plasma tHcy with AMI in the total study population was observed. When we stratified the population according to Vit-A tertiles, plasma tHcy was associated with acute myocardial infarction only in the upper Vit-A tertile (hazard ratio per SD: 1.25, 95% confidence interval: 1.04–1.53, pinteraction = 0.03). Conclusions The risk relationship between plasma tHcy and acute myocardial infarction was modified by serum concentrations of Vit-A in patients with suspected stable angina pectoris. This finding may clarify the relationship between tHcy and cardiovascular disease.

Dietary Choline Intake Is Directly Associated with Bone Mineral Density in the Hordaland Health Study

Background: Choline is an important nutrient either obtained from a variety of foods or synthesized endogenously, and it is the precursor of betaine. We previously reported positive associations between plasma free choline and bone mineral density (BMD). Animal studies suggest an impact of dietary choline on bone metabolism, but the role of dietary intake of choline and betaine for human bone health is unknown.Objectives: The main aims were to examine the associations of dietary choline, choline species, and betaine with BMD and to study the relations between dietary and plasma free choline and betaine.Methods: Study subjects were participants in the Hordaland Health Study, including 2649 women and 1983 men (aged 46-49 or 71-74 y). BMD was measured by dual-energy X-ray absorptiometry, and dietary intake was obtained by using a validated 169-item food-frequency questionnaire. Risk associations were assessed by logistic regression and correlations by ρ (Spearmans bivariate rank order correlation).Results: Subjects in the lowest compared with the highest tertile of dietary total choline, free choline, glycerophosphocholine, phosphocholine, phosphatidylcholine, and sphingomyelin had a higher risk of low-femoral neck BMD, defined as the lowest BMD quintile. Particularly strong associations were found among middle-aged men for intake of free choline (OR: 1.83; 95% CI: 1.24, 2.69; P = 0.002) and glycerophosphocholine (OR: 2.13; 95% CI: 1.43, 3.16; P < 0.001) and among elderly women for total choline (OR: 1.96; 95% CI: 1.33, 2.88; P = 0.001) and phosphatidylcholine (OR: 1.94; 95% CI: 1.33, 2.84: P = 0.001) intake. No significant associations were observed between dietary betaine and BMD. Dietary total choline, free choline, glycerophosphocholine, phosphatidylcholine, and sphingomyelin correlated weakly with plasma free choline (ρ: 0.07, 0.05, 0.07, 0.07, and 0.05, respectively; P < 0.01). Dietary betaine correlated with plasma betaine (ρ: 0.23; P < 0.001).Conclusion: Dietary choline was positively associated with BMD in middle-aged and elderly participants.