Association between plasma S-adenosy methionine and risk of mortality in patients with coronary artery disease: A cohort study

Background: S-adenosylmethionine (SAM) as methyl donors participates in methylation and is converted into S-adenosylhomocysteine (SAH), which is a precursor of homocysteine. Increased plasma SAH and homocysteine are associated with increased risk of cardiovascular disease. However, the relation of plasma SAM with cardiovascular risk is still unclear. Objectives: To determine the relation between plasma SAM and risk of mortality among patients with coronary artery disease (CAD). Methods: Baseline plasma SAM concentrations were measured in 1553 patients with CAD from the Guangdong Coronary Artery Disease Cohort between October 2008 and December 2011. Proportional hazards Cox analyses were performed to ascertain associations between SAM and risk of all-cause and cardiovascular mortality. Results: After a median follow-up of 9.2 (IQR: 8.5-10.2) y, of 1553 participants, 321 had died, including 227 deaths from cardiovascular diseases. Patients in the lowest quartile of SAM concentrations had a higher risk of all-cause death (HR, 1.59; 95% CI: 1.14. 2.21) and cardiovascular death (HR, 2.14; 95% CI: 1.41, 3.27) than those in the highest quartile in multivariable adjusted analysis. Each 1-SD decrease in the SAM concentration remained associated with a 42% greater risk of total death (HR, 1.42: 95% CI: 1.23, 1.64) and a 66% higher risk of cardiovascular death (HR, 1.66: 95% CI: 1.37, 2.01) after fully adjusting for other cardiovascular risk factors. Furthermore, each 1-SD decrease in plasma SAM/SAH ratio, as the methylation index, was also inversely associated with the risk of all-cause (HR, 1.80; 95% CI: 1.42. 2.29) and cardiovascular mortality (HR, 1.68; 95% CI: 1.29, 2.19) in fully adjusted analyses. Conclusions: Our data show a significant inverse relation between plasma SAM and risk of mortality in patients with CAD after adjustment for homocysteine, SAH, and other cardiovascular disease risk factors.