High concentration of symmetric dimethylarginine is associated with low platelet reactivity and increased bleeding risk in patients with acute coronary syndrome

Thromb Res. 2022 May:213:195-202. doi: 10.1016/j.thromres.2022.03.025. Epub 2022 Apr 3.

Abstract

Background: Dual antiplatelet therapy (DAPT) prevents ischemic events in patients with acute coronary syndrome (ACS), but is associated with increased risk of bleeding events. Symmetric dimethylarginine (SDMA) is one of nitric oxide (NO)-related pathway metabolites and stands as a promising biomarker of early chronic kidney disease (CKD) and cardiovascular diseases (CVDs).

Objectives: Our study evaluated the role of SDMA in predicting bleeding events in patients after ACS treated with DAPT.

Methods: We compared plasma concentrations of NO-related pathway metabolites in patients with ACS (n = 291) and investigated the prognostic value of SDMA as a bleeding predictor during 1-year follow-up. We measured the metabolites concentration using ultra performance liquid chromatography. Platelet reactivity was determined using impedance aggregometry.

Results: Patients with the highest quartile (4th) of SDMA concentration had significantly lower platelet aggregation compared to those in the 1st-3rd quartiles of SDMA, based on ADP + PGE1-, AA-, and ADP-induced platelet reactivity tests (p = 0.0004, p = 0.002, p = 0.014, respectively). Patients with major or minor bleeding events had significantly higher concentrations of SDMA as compared to those without bleeding events or to those with minimal bleeding events (p = 0.019, p = 0.019, respectively).

Conclusion: Higher SDMA concentration is associated with lower platelet reactivity and is associated with major and minor bleeding events in patients with ACS on DAPT. Therefore, SDMA stands as a potential biomarker for individualization of duration and potency of antiplatelet therapies in the ACS population at high risk of bleeding complications.

Keywords: Acute coronary syndrome; Bleeding; L-arginine; Nitric oxide; SDMA.

MeSH terms

  • Acute Coronary Syndrome* / complications
  • Acute Coronary Syndrome* / drug therapy
  • Adenosine Diphosphate
  • Arginine / analogs & derivatives
  • Biomarkers
  • Female
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Percutaneous Coronary Intervention* / adverse effects
  • Platelet Aggregation Inhibitors / adverse effects

Substances

  • Biomarkers
  • Platelet Aggregation Inhibitors
  • symmetric dimethylarginine
  • Adenosine Diphosphate
  • Arginine