Plasma Dimethylarginine Levels and Carotid Intima-Media Thickness are related to Atrial Fibrillation in Patients with Embolic Stroke

Int J Mol Sci. 2019 Feb 9;20(3):730. doi: 10.3390/ijms20030730.

Abstract

A relevant part of embolic strokes of undetermined source (ESUS) is assumed to be due to non-detected atrial fibrillation (AF). In this study, we aimed to investigate if markers of endothelial dysfunction and damage may indicate AF risk in embolic stroke. Eighty-eight patients with ischemic stroke confirmed by imaging were assigned to one of three groups: ESUS, AF, or micro-/macroangiopathy. ESUS patients underwent prolonged Holter electrocardiography scheduled for three days. The National Institutes of Health Stroke Scale (NIHSS), the CHA₂DS₂VASC score, and the carotid intima⁻media thickness (CIMT) were obtained. Markers of endothelial (dys)function (L-arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA)) were measured at day seven after stroke. ESUS patients were younger and had fewer cardiovascular risk factors than patients with determined stroke etiology. Compared with AF patients, ESUS patients showed significantly lower values of SDMA (p = 0.004) and higher values of L-arginine (p = 0.031), L-arginine/ADMA ratio (p = 0.006), L-arginine/SDMA ratio (p = 0.002), and ADMA/SDMA ratio (p = 0.013). Concordant differences could be observed comparing ESUS patients with those with newly diagnosed AF (p = 0.026; p = 0.03; p = 0.009; p = 0.004; and p = 0.046, respectively). CIMT was significantly larger in AF than in ESUS patients (p < 0.001), and was identified as an AF risk factor independent from CHA₂DS₂VASC in the regression analysis (p = 0.014). These findings may support future stratification for AF risk in patients who have suffered embolic stroke.

Keywords: ESUS; arginine; atrial fibrillation; dimethylarginine; embolic stroke; endothelial dysfunction; intima–media thickness.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Atrial Fibrillation / blood*
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / epidemiology
  • Atrial Fibrillation / etiology*
  • Biomarkers
  • Carotid Intima-Media Thickness*
  • Endothelium / metabolism
  • Endothelium / pathology
  • Female
  • Humans
  • Kidney Function Tests
  • Male
  • Middle Aged
  • ROC Curve
  • Risk Factors
  • Stroke / blood*
  • Stroke / complications*
  • Stroke / epidemiology
  • Stroke / etiology
  • Thromboembolism / etiology

Substances

  • Biomarkers
  • dimethylarginine
  • Arginine