Background: Asymmetrical dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, has been linked to cardiovascular risk. The clinical role of its structural isomer symmetrical dimethylarginine (SDMA) remains largely unclear.
Methods: We measured SDMA and ADMA in 3229 patients undergoing coronary angiography at baseline (1997-2000) and recorded total and cardiovascular mortality during a median follow-up time of 7.7 years. We investigated associations of SDMA with cardiovascular risk factors and mortality and compared its role as a cardiovascular risk factor with ADMA, which predicted mortality in previous analyses of our study.
Results: In linear regression analyses including common cardiovascular risk factors as covariates, SDMA and ADMA were significantly associated with cystatin C, N-terminal pro-B-type natriuretic peptide, New York Heart Association classification, and homocysteine. The regression coefficients were higher for SDMA than for ADMA. In Cox proportional-hazards models adjusted for cardiovascular risk factors, the hazard ratios (HRs) (with 95% CI) in the second, third, and fourth SDMA quartile compared to the lowest quartile were 0.77 (0.60-0.99), 0.99 (0.78-1.25), and 1.51 (1.20-1.91) for total mortality and 0.92 (0.68-1.25), 0.93 (0.68-1.26), and 1.54 (1.14-2.01) for cardiovascular mortality. The same calculations for ADMA quartiles revealed HRs of 1.05 (0.83-1.32), 1.19 (0.95-1.50), and 1.61 (1.30-1.99) for total mortality and HR of 1.00 (0.74-1.34), 1.26 (0.95-1.68), and 1.54 (1.18-2.02) for cardiovascular mortality.
Conclusions: Serum concentrations of SDMA are independently associated with increased cardiovascular and all-cause mortality in patients undergoing coronary angiography. The pattern of risk linked to SDMA is different from that linked to ADMA, suggesting different pathophysiological roles of these 2 methylarginine metabolites.