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

Cardiovascular Diabetology

Original Investigation

Tom Teerlink¹  Hans-Henrik Parving²  Bernt Johan von Scholten³  Henrik Reinhard³  Frederik Persson³  Tine W. Hansen³  Emilie H. Zobel³  Peter Rossing⁴  Peter K. Jacobsen⁵ 

[1] Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands;Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, 2820, Gentofte, Denmark;Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, 2820, Gentofte, Denmark;Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark;The Heart Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;

关键词: Microalbuminuria;    Type 2 diabetes;    Cardiovascular disease;    Macrovascular disease;    Symmetric dimethylarginine;    Asymmetric dimethylarginine;   

DOI  :  10.1186/s12933-017-0569-8

 received in 2017-04-27, accepted in 2017-06-23,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundTo 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.Methods200 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.ResultsHigher 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.ConclusionIn 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.

【 授权许可】

CC BY   
© The Author(s) 2017