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.
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.
Authors: T R Price; T A Manolio; R A Kronmal; S J Kittner; N C Yue; J Robbins; H Anton-Culver; D H O'Leary Journal: Stroke Date: 1997-06 Impact factor: 7.914
Authors: A Surdacki; M Nowicki; J Sandmann; D Tsikas; R H Boeger; S M Bode-Boeger; O Kruszelnicka-Kwiatkowska; F Kokot; J S Dubiel; J C Froelich Journal: J Cardiovasc Pharmacol Date: 1999-04 Impact factor: 3.105
Authors: Charles DeCarli; Joseph Massaro; Danielle Harvey; John Hald; Mats Tullberg; Rhoda Au; Alexa Beiser; Ralph D'Agostino; Philip A Wolf Journal: Neurobiol Aging Date: 2005-04 Impact factor: 4.673
Authors: R J MacAllister; H Parry; M Kimoto; T Ogawa; R J Russell; H Hodson; G S Whitley; P Vallance Journal: Br J Pharmacol Date: 1996-12 Impact factor: 8.739
Authors: R H Böger; S M Bode-Böger; A Szuba; P S Tsao; J R Chan; O Tangphao; T F Blaschke; J P Cooke Journal: Circulation Date: 1998-11-03 Impact factor: 29.690
Authors: A Vilar-Bergua; I Riba-Llena; C Nafría; A Bustamante; V Llombart; P Delgado; J Montaner Journal: J Cereb Blood Flow Metab Date: 2016-01 Impact factor: 6.200
Authors: Daniel Appel; Miriam Seeberger; Edzard Schwedhelm; Patrick Czorlich; Alwin E Goetz; Rainer H Böger; Juliane Hannemann Journal: Neurocrit Care Date: 2018-08 Impact factor: 3.210
Authors: Miklós Palkovits; Katarína Šebeková; Kristina Simon Klenovics; Anton Kebis; Gholamreza Fazeli; Udo Bahner; August Heidland Journal: PLoS One Date: 2013-06-20 Impact factor: 3.240
Authors: Shufen Chen; Na Li; Milani Deb-Chatterji; Qiang Dong; Jan T Kielstein; Karin Weissenborn; Hans Worthmann Journal: Int J Mol Sci Date: 2012-11-28 Impact factor: 5.923