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. 2017 Jul 11;16(1):88.
doi: 10.1186/s12933-017-0569-8.

Symmetric and asymmetric dimethylarginine as risk markers of cardiovascular disease, all-cause mortality and deterioration in kidney function in persons with type 2 diabetes and microalbuminuria

Emilie H Zobel  1 , Bernt Johan von Scholten  2 , Henrik Reinhard  2 , Frederik Persson  2 , Tom Teerlink  3 , Tine W Hansen  2 , Hans-Henrik Parving  4 , Peter K Jacobsen  5 , Peter Rossing  2   6
Affiliations

Symmetric and asymmetric dimethylarginine as risk markers of cardiovascular disease, all-cause mortality and deterioration in kidney function in persons with type 2 diabetes and microalbuminuria

Emilie H Zobel et al. Cardiovasc Diabetol. .

Abstract

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). C statistic (area under the curve) quantifies the model's improved ability to discriminate events from non-events. rIDI quantifies the increase in separation of events and non-events on a relative scale.

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 statistic was not significant for any of the endpoints for either SDMA or ADMA (p ≥ 0.10). 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 persons 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.

Keywords: Asymmetric dimethylarginine; Cardiovascular disease; Macrovascular disease; Microalbuminuria; Symmetric dimethylarginine; Type 2 diabetes.

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Figures

Fig. 1
Fig. 1
Correlation between symmetric and asymmetric dimethylarginine
Fig. 2
Fig. 2
Receiver operating characteristic (ROC) curves. Base model includes sex, age, systolic blood pressure, LDL-cholesterol, smoking, HbA1c, creatinine and urinary albumin excretion rate. Dashed line reference; Dotted line Base model; Full line Base model + symmetric dimethylarginine/asymmetric dimethylarginine
See this image and copyright information in PMC

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