Plasma Asymmetric Dimethylarginine and Adverse Events in Patients with Atrial Fibrillation Referred for Coronary Angiogram

Abstract

ObjectivesElevated plasma levels of asymmetric dimethylarginine (ADMA) have been reported to be associated with endothelial dysfunction, inflammation, and oxidative stress in multiple cardiovascular diseases. This study aimed to investigate whether ADMA was a predictor of clinical outcomes in atrial fibrillation (AF).Methods and ResultsFrom 2006-2009, 990 individuals were referred to our institution for coronary angiography. Among these patients, 141 subjects with a diagnosis of AF, including 52 paroxysmal AF (PAF) and 89 non-paroxysmal AF (non-PAF) patients, were identified as the study population. Plasma ADMA levels were measured. An adverse event was defined as the occurrence of ischemic stroke or cardiovascular death. The ADMA levels were higher in AF than non-AF patients (0.50±0.13 versus 0.45±0.07 µmol/L; p<0.001). Besides, non-PAF patients had higher ADMA levels than PAF patients (0.52±0.15 versus 0.48±0.08 µmol/L; p<0.001). During the follow-up of 30.7±14.4 months, 21 patients (14.9%) experienced adverse events, including cardiovascular death in 7 patients and ischemic stroke in 14. ADMA level, CHA2DS2-VASc score, and left atrial diameter were independent predictors of adverse events in the multivariate analysis. At a cutoff-value of 0.55 µmol/L, the Kaplan-Meier survival analysis showed that patients with a high ADMA level had a higher event rate during the follow-up period.ConclusionsA higher level of ADMA was a risk factor of adverse events in AF patients, which was independent from the CHA2DS2-VASc score. It deserves to further study whether ADMA could potentially refine the clinical risk stratification in AF.

Effect of asymmetric dimethylarginine (ADMA) on heart failure development

“…For examples, accumulation of ADMA occurs in hypertension (92), coronary disease (8,76,88,91), cardiac valve disease (2), idiopathic cardiomyopathy (3), congenital heart diseases (103), renal failure (54), diabetes (4,67), and atrial fibrillation (18,19) (Figure 3). Elevated plasma ADMA levels are associated with an increased risk for developing angina pectoris, myocardial infarction or cardiac death (9,10).…”

Asymmetric dimethylarginine, related arginine derivatives, and incident atrial fibrillation

“…37;38 Elevated blood concentrations of ADMA in AF indicate endothelial dysfunction and a prothrombotic milieu 39 that may account for adverse events in AF. 40 After restoration of sinus rhythm, circulating ADMA concentrations decrease, 17;41 and higher concentrations predict the recurrence of AF after ablation. 41;42 …”

“…14 ADMA and L-arginine have been associated with age, sex, body mass index, smoking, blood pressure, diabetes, and renal impairment. 11;43;44 In contrast to other, mostly smaller clinical samples that reported statistically significant associations of ADMA and AF phenotypes, 17;40;45 we applied rigorous adjustment for clinical risk factors that have been correlated with ADMA.…”

Effect of fish oil on circulating asymmetric dimethylarginine and adiponectin in overweight or obese patients with atrial fibrillation

“…Asymmetric dimethylarginine (ADMA), a major inhibitor of nitric oxide (NO) synthase, is another peptide secreted by adipocytes (Spoto, Parlongo, Parlongo, Sgro, & Zoccali, 2007), which can induce endothelial dysfunction, inflammation, and oxidative stress in cardiovascular disorders (Bouras et al, 2013). ADMA levels were significantly higher in AF compared to non‐AF individuals candidate for coronary angiography (Chao et al, 2013) and healthy controls (Cengel et al, 2008). Higher ADMA levels were associated with increased risk of AF recurrence following electrical cardioversion (Xia et al, 2008) and catheter ablation (Yang et al, 2011).…”

“…It has been suggested that ADMA could have prognostic value in predicting AF in high‐risk patients (Stamboul et al, 2015). Besides, studies have indicated the predictive value of ADMA in determining the adverse events such as mortality and stroke in AF (Chao et al, 2013; Horowitz et al, 2018).…”