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

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. (Stroke. 2009;40:2959-2964.)