Association of plasma ADMA levels with MRI markers of vascular brain injury: Framingham offspring study

Stroke. 2009 Sep;40(9):2959-64. doi: 10.1161/STROKEAHA.109.557116. Epub 2009 Jul 30.

Abstract

Background and purpose: Asymmetrical dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase, is a marker of endothelial dysfunction. Elevated circulating ADMA concentrations have been associated with systemic and carotid atherosclerosis, an elevated risk of developing stroke, and magnetic resonance imaging white-matter hyperintensities (WMHs). The relation of plasma ADMA to subclinical vascular brain injury has not been previously studied in a middle-aged, community-based sample.

Methods: In 2013 stroke-free Framingham offspring (mean+/-SD age, 58+/-9.5 years; 53% women), we related baseline plasma ADMA levels (1995-1998) to subsequent brain magnetic resonance imaging measures (1999-2004) of subclinical vascular injury: presence of silent brain infarcts (SBIs) and large white-matter hyperintensity volumes (LWMHs; defined as >1 SD above the age-specific mean).

Results: Prevalences of SBIs and LWMHs were 10.7% and 12.6%, respectively. In multivariable analyses adjusting for age, sex and traditional stroke risk factors, higher ADMA levels were associated with an increased risk of prevalent SBIs (odds ratio [OR] per 1-SD increase in ADMA=1.16; 95% CI, 1.01 to 1.33; P=0.04). We observed that participants in the upper 3 age-specific quartiles (Qs) of plasma ADMA values had an increased prevalence of SBIs (OR for Q2-Q4 vs Q1=1.43; 95% CI, 1.00 to 2.04; P<0.05). The prevalence of SBIs in Q1and Q2-Q4 was 8.3% and 11.6%, respectively. The prevalence of LWMHs did not differ according to ADMA concentrations.

Conclusions: Higher plasma ADMA values were associated with an increased prevalence of SBIs, after adjustment for traditional stroke risk factors. Thus, ADMA may be a potentially useful new biomarker of subclinical vascular brain injury, which is an important correlate of vascular cognitive impairment and risk of stroke.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Atherosclerosis / blood
  • Biomarkers / blood
  • Brain / diagnostic imaging*
  • Brain Infarction / blood*
  • Brain Infarction / diagnostic imaging*
  • Cohort Studies
  • Endothelium, Vascular / enzymology
  • Female
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type III / antagonists & inhibitors
  • Radiography
  • Risk Factors

Substances

  • Biomarkers
  • N,N-dimethylarginine
  • Arginine
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III