Inflammatory activation and endothelial dysfunction markers in patients with permanent atrial fibrillation: a cross-sectional study

Abstract

In recent years a growing body of evidence supported the role of inflammation in the initiation, maintenance and outcome of atrial fibrillation (AF). Nevertheless, despite a large amount of information, whether AF or the underlying structural heart disease (SHD) is the cause of the inflammatory process is still under debate. We, therefore, sought to determine if the inflammatory process reflect an underlying disease or the arrhythmia 'per se'. We evaluated plasma levels of soluble Interleukin 2 Receptor Alpha (sIL-2Rα), TNF-α and IL-18 in 100 consecutive patients with permanent AF, (43 with a SHD and 57 without a SHD) compared to 121 age and sex-matched controls which had normal sinus rhythm. We also evaluated the endothelial function in both groups of patients using reactive hyperemia index (RHI) values measured by Endo-PAT2000. Compared to controls, AF patients showed higher circulating levels of inflammatory markers and a lower mean value of RHI. At multiple logistic regression analysis, the inflammatory markers and RHI were significantly associated with AF presence, whereas ROC curve analysis had good sensitivity and specificity in inflammatory variables and RHI for AF presence. No significant association was observed in the group of permanent AF patients, between inflammatory markers and the presence of an underlying SHD. These findings could help to clarify the role of inflammation in subjects with AF and suggest that the markers of systemic inflammation are not associated with the underlying cardiovascular disease, rather with the atrial fibrillation 'per se'.

Keywords: atrial fibrillation; cytokines; endothelial dysfunction; inflammation; structural heart disease.

Figure 1

Plasma values of sIL-2Rα, IL-18, TNF-α and RHI values in atrial fibrillation subjects vs. controls. (A) Plasma values of sIL-2Rα in atrial fibrillation subjects compared with controls. (B) Plasma values of IL-18 in atrial fibrillation subjects compared with controls. (C) RHIvalues in atrial fibrillation subjects compared with controls. (D) Plasma values of TNF-α in atrial fibrillation subjects compared with controls.

Figure 2

Area under ROC curve, sensitivity and specificity of sIL-2Rα, IL-18, TNF-α and RHI in atrial fibrillation subjects. (A) Area under ROC curve, sensitivity and specificity of reactive hyperaemia index (RHI) in atrial fibrillation subjects. (B) Area under ROC curve, sensitivity and specificity of IL-18 in atrial fibrillation subjects. (C) Area under ROC curve, sensitivity and specificity of sIL-2Rα in atrial fibrillation subjects. (D) Area under ROC curve, sensitivity and specificity of TNF-α in atrial fibrillation subjects.