This Article Full Text Full Text (PDF) All Versions of this Article: 40/9/2959    most recent STROKEAHA.109.557116v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Pikula, A. Articles by Seshadri, S. PubMed PubMed Citation Articles by Pikula, A. Articles by Seshadri, S. Related Collections Risk Factors Epidemiology Endothelium/vascular type/nitric oxide

(Stroke. 2009;40:2959.)
© 2009 American Heart Association, Inc.

Original Contributions

Association of Plasma ADMA Levels With MRI Markers of Vascular Brain Injury

Framingham Offspring Study

Aleksandra Pikula, MD; Rainer H. Böger, MD; Alexa S. Beiser, PhD; Renke Maas, MD; Charles DeCarli, MD; Edzard Schwedhelm, PhD; Jayandra J. Himali, MSc; Friedrich Schulze, PhD; Rhoda Au, PhD; Margaret Kelly-Hayes, RN, DEd; Carlos S. Kase, MD; Ramachandran S. Vasan, MD; Philip A. Wolf, MD Sudha Seshadri, MD

From the Boston University Schools of Medicine and Public Health (A.P., A.S.B., J.J.H., R.A., M.H.-K., C.S.K., R.S.V., P.A.W., S.S.), Boston, Mass; Framingham Heart Study (A.P., A.S.B., R.A., M.H.-K., C.S.K., R.S.V., P.A.W., S.S.), Framingham, Mass; University of Hamburg (R.H.B., R.M., E.S., F.S.), Hamburg, and University of Erlangen-Nuremberg (R.M.), Nuremberg, Germany; and University of California at Davis (C.d.C.), Sacramento, Calif.

Correspondence and reprint requests to Dr Sudha Seshadri, Department of Neurology, Boston University School of Medicine, 715 Albany St, B-602, Boston, MA 02118-2526. E-mail suseshad{at}bu.edu

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.

Key Words: ADMA • endothelial dysfunction • silent cerebral infarct