Symmetric and Asymmetric Dimethylarginine as Risk Markers of Cardiovascular Disease, All-Cause Mortality, and Deterioration in Kidney Function in Patients with Type 2 Diabetes and Microalbuminuria

Background To evaluate symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) as risk markers of cardiovascular disease, all-cause mortality and deterioration in renal function in a well characterised type 2 diabetic population with microalbuminuria and without symptoms of coronary artery disease. Methods 200 participants followed for 6.1 years. SDMA and ADMA were measured at baseline. Endpoints included 1) composite cardiovascular endpoint (n=40); 2) all-cause mortality (n=26); and 3) decline in eGFR of >30% (n=42). Cox models were unadjusted and adjusted for traditional risk factors (sex, age, systolic blood pressure, LDL-cholesterol, smoking, HbA1c, creatinine and urinary albumin excretion rate). To assess if SDMA or ADMA improved risk prediction beyond traditional risk factors we calculated c-statistics and relative integrated discrimination improvement (rIDI). Results Higher SDMA was associated with increased risk of all three endpoints (unadjusted: p≤0.001; adjusted: p≤0.02). Higher ADMA was associated with all-cause mortality (unadjusted: p=0.002; adjusted: p=0.006), but not cardiovascular disease or decline in eGFR(p≥0.29).The c-statistics was not significant for any of the endpoint for either SDMA or ADMA (p≥0.11). The rIDI for SDMA was 15.0%(p=0.081) for the cardiovascular endpoint, 52.5%(p=0.025) for all-cause mortality and 48.8%(p=0.007) for decline in eGFR; for ADMA the rIDI was 49.1%(p=0.017) for all-cause mortality. Conclusion In patients with type 2 diabetes and microalbuminuria higher SDMA was associated with incident cardiovascular disease, all-cause mortality and deterioration in renal function. Higher ADMA was associated with all-cause mortality. SDMA and ADMA significantly improved risk prediction for all-cause mortality, and SDMA for deterioration in renal function beyond traditional risk factors.