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.