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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albuminuria / complications
  • Albuminuria / diagnosis
  • Albuminuria / metabolism*
  • Arginine / analogs & derivatives*
  • Arginine / metabolism
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / mortality*
  • Coronary Disease / diagnosis
  • Creatinine / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Glomerular Filtration Rate / physiology
  • Humans
  • Kidney / physiopathology*
  • Male
  • Middle Aged
  • Risk Factors

Substances

  • dimethylarginine
  • symmetric dimethylarginine
  • Arginine
  • Creatinine