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  •    AF strongly associated with inflammation but not oxidative stress
    Venkata M. Alla M.D., Creighton University, Omaha.

    The association between inflammation and atrial fibrillation (AF) is well established. Emerging evidence also supports the role of oxidative stress in the initiation and maintenance of AF. In this study Li et al. attempt to establish this association using a number of biomarkers. The study included 305 patients with AF prospectively enrolled in the Vanderbilt AF registry and 150 control subjects without known inflammatory disorders or arrhythmias. Patients with AF were stratified as paroxysmal, persistent or permanent AF based on standard definitions. Further stratification into lone AF (age≤65years and without hypertension, diabetes, heart failure, ischemic or other structural heart disease within 2 years of AF onset) and typical AF was also done.  The inflammatory markers included in the study were IL-6, IL-8, IL-10, TNF-α, and monocyte chemoattractant protein 1 (MCP-1). Urinary F2-isoprostane was used as an index of oxidative stress. Vascular endothelial growth factor (VEGF) and N-terminal- pro-brain natriuretic peptide (NTpBNP) were the other measured biomarkers. A onetime measurement of the aforementioned markers at the time of entry into the registry was used for all analyses. Not surprisingly, patients with AF were older, more often men, and had a higher frequency of hypertension, diabetes, ischemic heart disease and heart failure. All the inflammatory markers were significantly higher in patients with AF compared to controls after adjustment for age, sex and other known confounders like heart failure. This was true even for the subgroup of patients with lone AF. However, there was no significant difference between the levels of inflammatory markers among patients with lone AF compared to typical AF indicating that the level of inflammation was similar between these 2 groups. In contrast, IL-10, TNF-α and NTpBNP showed a graded increase from paroxysmal through persistent and permanent AF. Surprisingly, there was no difference in the levels of urinary F2-isoprostane between controls and AF patients. The authors conclude that there is strong independent association between AF and inflammation and that this inflammatory response is unlikely to be a result of oxidative stress.

    The role of oxidative stress in AF is a topic of active research and our understanding continues to evolve. Prior studies have documented increase in markers like nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and decreased AF with therapies targeting oxidative mechanisms like vitamin C.  Markers used to assess oxidative stress and the methods used vary widely with some studies using intracardiac serum samples and others assessing peripheral blood.  Thus far, evidence supporting the role of oxidative stress appears strongest in post-cardiac surgery AF patients particularly when measures of local myocardial oxidative stress rather than systemic measures were used for assessment. Proposed mechanisms for AF susceptibility include reactive oxidant species induced lipid peroxidation, breakdown of cell membrane, decreased mitochondrial function, calcium overload and apoptosis leading to structural remodeling and electrical remodeling like decreased atrial effective refractory period. 

    A major limitation of the current study is its cross sectional design and one time measurement of the various markers. Majority of the patients included in the study had paroxysmal AF and were not necessarily in AF at the time of measurement of urinary F2-isoprostanes. This is likely to have decreased the sensitivity of the study. Though this study demonstrated a strong association between AF and inflammation, its design does not allow us to draw any conclusions on causality or mechanisms, hence providing no new insights into this aspect. In summary, this study provides support to the link between inflammation but does not support the association between AF and oxidative stress in this selected group of patients.  Further studies assessing the role of oxidative stress in AF using multiple markers particularly those that reflect local myocyte oxidative stress (rather than systemic) are necessary. 


    Li J, Solus J, Chen Q, Rho YH, Milne G, Stein CM, Darbar D. Role of inflammation and oxidative stress in atrial fibrillation. Heart Rhythm. 2010 Apr;7(4):438-44.

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