Asymmetric Dimethylarginine Levels are Highly Associated With Atrial Fibrillation in an Elderly Population

Abstract

BackgroundThe importance of endothelial dysfunction in atrial fibrillation (AF) is not clarified. The aim of this study was to evaluate endothelial dysfunction assessed by selected inflammatory and haemostatic endothelial markers and nitric oxide (NO) associated variables as related to the presence of AF in an elderly population. NO is known to express anti-thrombotic as well as vasoactive properties.MethodsThis is a cross sectional study of 75-year old subjects with AF (n = 62) and control subjects in sinus rhythm (n = 124), matched for gender. Fasting blood samples were collected for analyses of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO-synthase, L-arginine, E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor (vWF).ResultsLevels of vWF and ADMA were significantly higher in AF patients vs controls (P = 0.023 and P < 0.001, respectively) and the L-arginine/ADMA ratios were lower (P = 0.015), the latters still significant after adjustment for relevant covariates (P = 0.007 and P = 0.037, respectively). No significant differences in the levels of VCAM-1 and E-selectin were observed between the groups. When dividing the ADMA levels into quartiles there was a significant trend for having AF with increasing levels of ADMA (P < 0.001) with a cut-off at the 25th percentile (< 0.54 µmol/L), giving an adjusted OR for having AF of 12.46 (95% CI 3.11 - 49.86) (P < 0.001) with higher levels. A similar inverse trend was seen for the L-arginine/ADMA ratio.ConclusionOur population of 75-year-old AF patients had significantly impaired endothelial function assessed by increased levels of vWF, and more pronounced by high levels of ADMA. The results indicate AF in the elderly to be closely associated with the regulatory pathway of NO.

Soluble vascular cell adhesion molecule-1 in patients with non-valvular atrial fibrillation

“…ROC curve for prediction of all-cause mortality by sVCAM-1 in both study groups tration was higher than in healthy controls, although this adhesion molecule lost its significance as a predictor of AF in multifactorial analysis. Seljeflot et al [7] found impaired endothelial function, expressed by higher blood vWF and ADMA concentrations, in patients with AF who were over the age of 75 compared to an age-matched control group with sinus rhythm. However, similar to our results (Tab.…”

“…The role of endothelial dysfunction in patients with atrial fibrillation remains understudied [3][4][5][6][7]. However, it has been reported that the combined dysfunction of cardiac (i.e.…”

“…endocardial, microvascular and coronary) and vascular endothelial cells may affect atrial and ventricular cardiomyocyte contractility and remodelling and lead to fibrosis. Endothelial dysfunction may also lead to reduced synthesis of substances with antithrombotic, anti-inflammatory and anti-proliferative properties, such as tissue plasminogen activator and nitric oxide (due, i.a., to an increased level of the amino acid asymmetric dimethylarginine [ADMA], an endogenous inhibitor of NO synthase [eNOS]) [7], as well as to increased secretion of procoagulant factors, e.g. von Willebrand factor (VWF) [7], overexpression of adhesion molecules (e.g.…”

“…Endothelial dysfunction may also lead to reduced synthesis of substances with antithrombotic, anti-inflammatory and anti-proliferative properties, such as tissue plasminogen activator and nitric oxide (due, i.a., to an increased level of the amino acid asymmetric dimethylarginine [ADMA], an endogenous inhibitor of NO synthase [eNOS]) [7], as well as to increased secretion of procoagulant factors, e.g. von Willebrand factor (VWF) [7], overexpression of adhesion molecules (e.g. sVCAM, sICAM, P-selectin and E-selectin) [5], and increase of growth factors (e.g.…”

“…fibroblast growth factor [bFGF] and vascular endothelial growth factor [VEGF]) [3]. Through the pathomechanisms mentioned, endocardial and vascular endothelial dysfunction may take part in the pathogenesis of AF occurrence, recurrence of arrhythmia, the formation of permanent forms of AF, and risk of thromboembolic complications [3][4][5][6][7][8].…”